Skip to main content
SpringerLink
Log in

Introduction

  • Chapter
  • First Online:
CPP, Cell-Penetrating Peptides

  • 950 Accesses

Abstract

The genesis of cell-penetrating peptide research (CPP ; also known as protein/peptide transduction domains, PTD , or Trojan peptides ) was born from the publication of two parallel landmark reports on an HIV tat trans-activator protein, now widely known to epitomise membrane shuttling proteins (but not to be confused with the shuttling proteins cycling back and forth through the nuclear pore complex).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adachi, Y., Sakamoto, K., Umemoto, T., Fukuda, Y., Tani, A., & Asami, T. (2017). Investigation on cellular uptake and pharmacodynamics of DOCK2-inhibitory peptides conjugated with cell-penetrating peptides. Bioorganic & Medicinal Chemistry, 25, 2148–2155.

    Article  CAS  Google Scholar 

  • Akishiba, M., Takeuchi, T., Kawaguchi, Y., Sakamoto, K., Yu, H. H., Nakase, I., et al. (2017). Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide. Nature Chemistry, 9, 751–761.

    Article  CAS  PubMed  Google Scholar 

  • Alaybeyoglu, B., Uluocak, B. G., Akbulut, B. S., & Ozkirimli, E. (2017). The effect of a beta-lactamase inhibitor peptide on bacterial membrane structure and integrity: A comparative study. Journal of Peptide Science, 23, 374–383.

    Article  CAS  PubMed  Google Scholar 

  • Alberici, L., Roth, L., Sugahara, K. N., Agemy, L., Kotamraju, V. R., Teesalu, T., et al. (2013). De novo design of a tumor-penetrating peptide. Cancer Research, 73, 804–812.

    CAS  PubMed  Google Scholar 

  • Alexander-Bryant, A. A., Dumitriu, A., Attaway, C. C., Yu, H., & Jakymiw, A. (2015). Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo. Journal of Controlled Release: Official Journal of the Controlled Release Society, 218, 72–81.

    Article  CAS  Google Scholar 

  • Alhakamy, N. A., Kaviratna, A., Berkland, C. J., & Dhar, P. (2013). Dynamic measurements of membrane insertion potential of synthetic cell penetrating peptides. Langmuir: The ACS Journal of Surfaces and Colloids, 29, 15336–15349.

    Article  CAS  Google Scholar 

  • Alta, R. Y. P., Vitorino, H. A., Goswami, D., Liria, C. W., Wisnovsky, S. P., Kelley, S. O., et al. (2017). Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron. PLoS ONE, 12, e0171729.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Andreev, O. A., Engelman, D. M., & Reshetnyak, Y. K. (2010). pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents. Molecular Membrane Biology, 27, 341–352.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Antunes, E., Azoia, N. G., Matama, T., Gomes, A. C., & Cavaco-Paulo, A. (2013). The activity of LE10 peptide on biological membranes using molecular dynamics, in vitro and in vivo studies. Colloids and Surfaces B, Biointerfaces, 106, 240–247.

    Article  CAS  PubMed  Google Scholar 

  • Arukuusk, P., Pärnaste, L., Oskolkov, N., Copolovici, D. M., Margus, H., Padari, K., et al. (2013). New generation of efficient peptide-based vectors, NickFects, for the delivery of nucleic acids. Biochimica et Biophysica Acta, 1828, 1365–1373.

    Article  CAS  PubMed  Google Scholar 

  • Bae, H. D., Lee, J., Jin, X. H., & Lee, K. (2016). Potential of translationally controlled tumor protein-derived protein transduction domains as antigen carriers for nasal vaccine delivery. Molecular Pharmaceutics, 13, 3196–3205.

    Article  CAS  PubMed  Google Scholar 

  • Bahnsen, J. S., Franzyk, H., Sayers, E. J., Jones, A. T., & Nielsen, H. M. (2015). Cell-penetrating antimicrobial peptides—prospectives for targeting intracellular infections. Pharmaceutical Research, 32, 1546–1556.

    Article  CAS  PubMed  Google Scholar 

  • Bang, J. Y., Kim, E. Y., Kang, D. K., Chang, S. I., Han, M. H., Baek, K. H., et al. (2011). Pharmacoproteomic analysis of a novel cell-permeable peptide inhibitor of tumor-induced angiogenesis. Molecular & Cellular Proteomics: MCP, 10(M110), 005264.

    PubMed  Google Scholar 

  • Bartlett 2ND, R. L., Sharma, S., & Panitch, A. (2013). Cell-penetrating peptides released from thermosensitive nanoparticles suppress pro-inflammatory cytokine response by specifically targeting inflamed cartilage explants. Nanomedicine: Nanotechnology, Biology, and Medicine, 9, 419–427.

    Google Scholar 

  • Basu, S., & Wickstrom, E. (1997). Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconjugate Chemistry, 8, 481–488.

    Article  CAS  PubMed  Google Scholar 

  • Bechara, C., Pallerla, M., Zaltsman, Y., Burlina, F., Alves, I. D., Lequin, O., et al. (2013). Tryptophan within basic peptide sequences triggers glycosaminoglycan-dependent endocytosis. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 27, 738–749.

    Article  CAS  Google Scholar 

  • Bera, S., Kar, R. K., Mondal, S., Pahan, K., & Bhunia, A. (2016). Structural elucidation of the cell-penetrating penetratin peptide in model membranes at the atomic level: Probing hydrophobic interactions in the blood-brain barrier. Biochemistry, 55, 4982–4996.

    Article  CAS  PubMed  Google Scholar 

  • Bergmann, R., Splith, K., Pietzsch, J., Bachmann, M., & Neundorf, I. (2017). Biological characterization of novel nitroimidazole-peptide conjugates in vitro and in vivo. Journal of Peptide Science, 23, 597–609.

    Article  CAS  PubMed  Google Scholar 

  • Betts, C., Saleh, A. F., Arzumanov, A. A., Hammond, S. M., Godfrey, C., Coursindel, T., et al. (2012). Pip6-PMO, a new generation of peptide-oligonucleotide conjugates with improved cardiac exon skipping activity for DMD treatment. Molecular Therapy—Nucleic Acids, 1, e38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bi, X., Wang, C., Dong, W., Zhu, W., & Shang, D. (2014). Antimicrobial properties and interaction of two Trp-substituted cationic antimicrobial peptides with a lipid bilayer. The Journal of Antibiotics, 67, 361–368.

    Article  CAS  PubMed  Google Scholar 

  • Bonny, C., Oberson, A., Negri, S., Sauser, C., & Schorderet, D. F. (2001). Cell-permeable peptide inhibitors of JNK: Novel blockers of beta-cell death. Diabetes, 50, 77–82.

    Article  CAS  PubMed  Google Scholar 

  • Brezden, A., Mohamed, M. F., Nepal, M., Harwood, J. S., Kuriakose, J., Seleem, M. N., et al. (2016). Dual targeting of intracellular pathogenic bacteria with a cleavable conjugate of Kanamycin and an antibacterial cell-penetrating Peptide. Journal of the American Chemical Society, 138, 10945–10949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camarero, J. A. (2017). Cyclotides, a versatile ultrastable micro-protein scaffold for biotechnological applications. Bioorganic & Medicinal Chemistry Letters, 27, 5089–5099.

    Article  CAS  Google Scholar 

  • Cao, X. W., Yang, X. Z., Du, X., Fu, L. Y., Zhang, T. Z., Shan, H. W., et al. (2018). Structure optimization to improve the delivery efficiency and cell selectivity of a tumor-targeting cell-penetrating peptide. Journal of Drug Targeting, 1–28.

    Google Scholar 

  • Cerrato, C. P., Pirisinu, M., Vlachos, E. N., & Langel, Ü. (2015). Novel cell-penetrating peptide targeting mitochondria. FASEB Journal, 29, 4589–4599.

    Article  CAS  PubMed  Google Scholar 

  • Chee, S. M., Wongsantichon, J., Soo Tng, Q., Robinson, R., Joseph, T. L., Verma, C., et al. (2014). Structure of a stapled peptide antagonist bound to nutlin-resistant Mdm2. PLoS One, 9, e104914.

    Google Scholar 

  • Chen, H., Li, X., Liu, F., Zhang, H., & Wang, Z. (2017a). Renal Clearable peptide functionalized NaGdF4 nanodots for high-efficiency tracking orthotopic colorectal tumor in mouse. Molecular Pharmaceutics, 14, 3134–3141.

    Article  CAS  PubMed  Google Scholar 

  • Chen, G., Ma, B., Xie, R., Wang, Y., Dou, K., & Gong, S. (2017a). NIR-induced spatiotemporally controlled gene silencing by upconversion nanoparticle-based siRNA nanocarrier. Journal of Controlled Release.

    Google Scholar 

  • Chen, Y., Shen, Y., Guo, X., Zhang, C., Yang, W., Ma, M., et al. (2006). Transdermal protein delivery by a coadministered peptide identified via phage display. Nature Biotechnology, 24, 455–460.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Y., Zhang, M., Jin, H., Tang, Y., Wang, H., Xu, Q., et al. (2017c). Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature. Biomaterials, 116, 57–68.

    Article  CAS  PubMed  Google Scholar 

  • Chen, L., Zhang, Q., Yuan, X., Cao, Y., Yuan, Y., Yin, H., et al. (2017d). How charge distribution influences the function of membrane-active peptides: Lytic or cell-penetrating? The International Journal of Biochemistry & Cell Biology, 83, 71–75.

    Article  CAS  Google Scholar 

  • Chopra, A. (2012). LTVSPWY peptide-modified PEGylated chitosan magnetic nanoparticles. Molecular Imaging and Contrast Agent Database (MICAD). Bethesda (MD).

    Google Scholar 

  • Chuah, J. A., Matsugami, A., Hayashi, F., & Numata, K. (2016). Self-assembled peptide-based system for mitochondrial-targeted gene delivery: Functional and structural insights. Biomacromolecules, 17, 3547–3557.

    Article  CAS  PubMed  Google Scholar 

  • Chuah, J. A., Yoshizumi, T., Kodama, Y., & Numata, K. (2015a). Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based carriers. Scientific Reports, 5, 7751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuah, J. A., Yoshizumi, T., Kodama, Y., & Numata, K. (2015b). Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based carriers. Scientific Reports, 5, 7751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collado Camps, E., & Brock, R. (2017). An opportunistic route to success: Towards a change of paradigm to fully exploit the potential of cell-penetrating peptides. Bioorganic & Medicinal Chemistry.

    Google Scholar 

  • Conlon, J. M., Mechkarska, M., Prajeep, M., Arafat, K., Zaric, M., Lukic, M. L., et al. (2013). Transformation of the naturally occurring frog skin peptide, alyteserin-2a into a potent, non-toxic anti-cancer agent. Amino Acids, 44, 715–723.

    Article  CAS  PubMed  Google Scholar 

  • Crombez, L., Aldrian-Herrada, G., Konate, K., Nguyen, Q. N., McMaster, G. K., Brasseur, R., et al. (2009a). A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells. Molecular Therapy, 17, 95–103.

    Article  CAS  PubMed  Google Scholar 

  • Crombez, L., Morris, M. C., Dufort, S., Aldrian-Herrada, G., Nguyen, Q., Mc Master, G., et al. (2009b). Targeting cyclin B1 through peptide-based delivery of siRNA prevents tumour growth. Nucleic Acids Research, 37, 4559–4569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daly, N. L., Love, S., Alewood, P. F., & Craik, D. J. (1999). Chemical synthesis and folding pathways of large cyclic polypeptides: Studies of the cystine knot polypeptide kalata B1. Biochemistry, 38, 10606–10614.

    Article  CAS  PubMed  Google Scholar 

  • Dasari, B. C., Cashman, S. M., & Kumar-Singh, R. (2017). Reducible PEG-POD/DNA Nanoparticles for gene transfer in vitro and in vivo: Application in a mouse model of age-related macular degeneration. Molecular Therapy—Nucleic Acids, 8, 77–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Datta, G., Chaddha, M., Garber, D. W., Chung, B. H., Tytler, E. M., Dashti, N., et al. (2000). The receptor binding domain of apolipoprotein E, linked to a model class A amphipathic helix, enhances internalization and degradation of LDL by fibroblasts. Biochemistry, 39, 213–220.

    Article  CAS  PubMed  Google Scholar 

  • de Coupade, C., Fittipaldi, A., Chagnas, V., Michel, M., Carlier, S., Tasciotti, E., et al. (2005). Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules. The Biochemical Journal, 390, 407–418.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de la Torre, C., Dominguez-Berrocal, L., Murguia, J. R., Marcos, M. D., Martinez-Manez, R., Bravo, J., et al. (2017). Polylysine-capped mesoporous silica nanoparticles as carrier of the C9h peptide to induce apoptosis in cancer cells. Chemistry.

    Google Scholar 

  • Demeule, M., Regina, A., Che, C., Poirier, J., Nguyen, T., Gabathuler, R., et al. (2008). Identification and design of peptides as a new drug delivery system for the brain. The Journal of Pharmacology and Experimental Therapeutics, 324, 1064–1072.

    Article  CAS  PubMed  Google Scholar 

  • Derossi, D., Joliot, A. H., Chassaing, G., & Prochiantz, A. (1994). The third helix of the Antennapedia homeodomain translocates through biological membranes. Journal of Biological Chemistry, 269, 10444–10450.

    CAS  PubMed  Google Scholar 

  • Derouazi, M., Di Berardino-Besson, W., Belnoue, E., Hoepner, S., Walther, R., Benkhoucha, M., et al. (2015). Novel Cell-penetrating peptide-based vaccine induces robust CD4+ and CD8+ T Cell-mediated antitumor immunity. Cancer Research, 75, 3020–3031.

    Article  CAS  PubMed  Google Scholar 

  • Desai, P. R., Cormier, A. R., Shah, P. P., Patlolla, R. R., Paravastu, A. K., & Singh, M. (2014). (31)P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 86, 190–199.

    Google Scholar 

  • Deshayes, S., Morris, M. C., Divita, G., & Heitz, F. (2005). Interactions of primary amphipathic cell penetrating peptides with model membranes: Consequences on the mechanisms of intracellular delivery of therapeutics. Current Pharmaceutical Design, 11, 3629–3638.

    Article  CAS  PubMed  Google Scholar 

  • Dias, S. A., Freire, J. M., Perez-Peinado, C., Domingues, M. M., Gaspar, D., Vale, N., et al. (2017). New potent membrane-targeting antibacterial peptides from viral capsid proteins. Frontiers in Microbiology, 8, 775.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dietrich, L., Rathmer, B., Ewan, K., Bange, T., Heinrichs, S., Dale, T. C., et al. (2017). Cell permeable stapled peptide inhibitor of WNT signaling that targets beta-catenin protein-protein interactions. Cell Chemical Biology, 24, 958–968.

    Article  CAS  PubMed  Google Scholar 

  • Dixon, J. E., Osman, G., Morris, G. E., Markides, H., Rotherham, M., Bayoussef, Z., et al. (2016). Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides. Proceedings of the National Academy of Sciences of the United States of America, 113, 5.

    Article  CAS  Google Scholar 

  • Dong, H., Zhang, Y., Song, L., Kim, D. S., Wu, H., Yang, L., et al. (2016). Cell-permeable peptide blocks TLR4 Signaling and Improves Islet Allograft Survival. Cell Transplantation, 25, 1319–1329.

    Article  PubMed  Google Scholar 

  • Duchardt, F., Ruttekolk, I. R., Verdurmen, W. P., Lortat-Jacob, H., Burck, J., Hufnagel, H., et al. (2009). A cell-penetrating peptide derived from human lactoferrin with conformation-dependent uptake efficiency. The Journal of Biological Chemistry, 284, 36099–36108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eggenberger, K., Birtalan, E., Schroder, T., Brase, S., & Nick, P. (2009). Passage of Trojan peptoids into plant cells. Chembiochem: A European Journal of Chemical Biology, 10, 2504–2512.

    Article  CAS  PubMed  Google Scholar 

  • Ehrenreich, B. A., & Cohn, Z. A. (1969). The fate of peptides pinocytosed by macrophages in vitro. Journal of Experimental Medicine, 129, 227–245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El-Andaloussi, S., Johansson, H. J., Holm, T., & Langel, Ü. (2007). A novel cell-penetrating peptide, M918, for efficient delivery of proteins and peptide nucleic acids. Molecular Therapy: The Journal of the American Society of Gene Therapy, 15, 1820–1826.

    Article  CAS  Google Scholar 

  • EL-andaloussi, S., Lehto, T., Mäger, I., Rosenthal-Aizman, K., Oprea, I.I., Simonson, O. E., et al. (2011). Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo. Nucleic Acids Research, 39, 3972–3987.

    Article  CAS  PubMed Central  Google Scholar 

  • Elliott, G., & O’Hare, P. (1997). Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell, 88, 223–233.

    Article  CAS  PubMed  Google Scholar 

  • Elmquist, A., Lindgren, M., Bartfai, T., & Langel, Ü. (2001). VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions. Experimental Cell Research, 269, 237–244.

    Article  CAS  PubMed  Google Scholar 

  • Esbjörner, E. K., Oglȩcka, K., Lincoln, P., Gräslund, A., & Nordén, B. (2007). Membrane binding of pH-sensitive influenza fusion peptides. Positioning, configuration, and induced leakage in a lipid vesicle Model†. Biochemistry, 46, 13490–13504.

    Article  PubMed  CAS  Google Scholar 

  • Eudes, F., & Macmillan, T. (2014). Organelle Targeting Nanocarriers. Google Patents.

    Google Scholar 

  • Ezzat, K., Andaloussi, S. E., Zaghloul, E. M., Lehto, T., Lindberg, S., Moreno, P. M., et al. (2011). PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation. Nucleic Acids Research, 39, 5284–5298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan, L. Q., Du, G. X., Li, P. F., Li, M. W., Sun, Y., & Zhao, L. M. (2016). Improved breast cancer cell-specific intracellular drug delivery and therapeutic efficacy by coupling decoration with cell penetrating peptide and SP90 peptide. Biomedicine & pharmacotherapy = Biomedecine & Pharmacotherapie, 84, 1783–1791.

    Google Scholar 

  • Fawell, S., Seery, J., Daikh, Y., Moore, C., Chen, L. L., Pepinsky, B., et al. (1994). Tat-mediated delivery of heterologous proteins into cells. Proceedings of the National Academy of Sciences of the United States of America, 91, 664–668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandez Masso, J. R., Oliva Arguelles, B., Tejeda, Y., Astrada, S., Garay, H., Reyes, O., et al. (2013). The antitumor peptide CIGB-552 increases COMMD1 and inhibits growth of human lung cancer cells. Journal of Amino Acids, 2013, 251398.

    Google Scholar 

  • Fletcher, T. C., Digiandomenico, A., & Hawiger, J. (2010). Extended anti-inflammatory action of a degradation-resistant mutant of cell-penetrating suppressor of cytokine signaling 3. The Journal of Biological Chemistry, 285, 18727–18736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fogal, V., Zhang, L., Krajewski, S., & Ruoslahti, E. (2008). Mitochondrial/cell-surface protein p32/gC1qR as a molecular target in tumor cells and tumor stroma. Cancer Research, 68, 7210–7218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55, 1189–1193.

    Article  CAS  PubMed  Google Scholar 

  • Freimann, K., Arukuusk, K., Kurrikoff, K., Vasconselos, L. D. F., Veiman, K.-L., Uusna, J., et al. (2016). Optimization of in vivo pDNA gene delivery with NickFect peptide vectors. Jouranal of Controlled Release, 241, 135–143.

    Article  CAS  PubMed  Google Scholar 

  • Freire, J. M., Veiga, A. S., Rego de Figueiredo, I., de la Torre, B. G., Santos, N. C., Andreu, D., et al. (2014). Nucleic acid delivery by cell penetrating peptides derived from dengue virus capsid protein: Design and mechanism of action. The FEBS Journal, 281, 191–215.

    Article  PubMed  CAS  Google Scholar 

  • Fu, L. S., Wu, Y. R., Fang, S. L., Tsai, J. J., Lin, H. K., Chen, Y. J., et al. (2017). Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation. Sci Rep, 7, 12352.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fuselier, T., & Wimley, W. C. (2017). Spontaneous Membrane Translocating Peptides: The Role of Leucine-Arginine Consensus Motifs. Biophysical Journal, 113, 835–846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Futaki, S. (2006). Oligoarginine vectors for intracellular delivery: Design and cellular-uptake mechanisms. Biopolymers, 84, 241–249.

    Article  CAS  PubMed  Google Scholar 

  • Galdiero, S., Falanga, A., Morelli, G., & Galdiero, M. (2015). gH625: A milestone in understanding the many roles of membranotropic peptides. Biochimica et Biophysica Acta, 1, 16–25.

    Article  CAS  Google Scholar 

  • Gautam, A., Nanda, J. S., Samuel, J. S., Kumari, M., Priyanka, P., Bedi, G., et al. (2016). Topical Delivery of Protein and Peptide Using Novel Cell Penetrating Peptide IMT-P8. Scientific Reports, 6.

    Google Scholar 

  • Gehrmann, M., Stangl, S., Foulds, G. A., Oellinger, R., Breuninger, S., Rad, R., et al. (2014). Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide. PLoS ONE, 9, e105344.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gennari, C. G., Franze, S., Pellegrino, S., Corsini, E., Vistoli, G., Montanari, L., et al. (2016). Skin Penetrating peptide as a tool to enhance the permeation of heparin through human epidermis. Biomacromolecules, 17, 46–55.

    Article  CAS  PubMed  Google Scholar 

  • Goldfarb, D. S. (1991). Shuttling proteins go both ways. Current Biology, 1, 212–214.

    Article  CAS  PubMed  Google Scholar 

  • Gomarasca, M., T, F. C. M., Greune, L., Hardwidge, P. R., SCHMIDT, M. A. & RUTER, C. 2017. Bacterium-derived cell-penetrating peptides deliver gentamicin to kill intracellular pathogens. Antimicrobial Agents and Chemotherapy, 61.

    Google Scholar 

  • Gong, Z., Walls, M. T., Karley, A. N., & Karlsson, A. J. (2016). Effect of a flexible linker on recombinant expression of cell-penetrating peptide fusion proteins and their translocation into fungal cells. Molecular Biotechnology, 58, 838–849.

    Article  CAS  PubMed  Google Scholar 

  • Gopalakrishnan, S., Pandey, N., Tamiz, A. P., Vere, J., Carrasco, R., Somerville, R., et al. (2009). Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer. International Journal of Pharmaceutics, 365, 121–130.

    Article  CAS  PubMed  Google Scholar 

  • Green, M., & Loewenstein, P. M. (1988). Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell, 55, 1179–1188.

    Article  CAS  PubMed  Google Scholar 

  • Greer, K. L., Lochmuller, H., Flanigan, K., Fletcher, S., & Wilton, S. D. (2014). Targeted exon skipping to correct exon duplications in the dystrophin gene. Molecular Therapy. Nucleic Acids, 3, e155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Griffin, J. I., Cheng, S. K. K., Hayashi, T., Carson, D., Saraswathy, M., Nair, D. P., et al. (2017). Cell-penetrating peptide CGKRK mediates efficient and widespread targeting of bladder mucosa following focal injury. Nanomedicine, 13, 1925–1932.

    Article  CAS  PubMed  Google Scholar 

  • Gronewold, A., Horn, M., Randelovic, I., Tovari, J., Munoz Vazquez, S., et al. (2017). Characterization of a cell-penetrating peptide with potential anticancer activity. ChemMedChem, 12, 42–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guilhelmelli, F., Vilela, N., Albuquerque, P., Derengowski, L. D. S., & Kyaw, C. M. (2013). Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of becterial resistance. Frontiers in Microbiology, 4, article 353, 1–12.

    Google Scholar 

  • Gupta, A., Mandal, D., Ahmadibeni, Y., Parang, K., & Bothun, G. (2011). Hydrophobicity drives the cellular uptake of short cationic peptide ligands. European Biophysics Journal: EBJ, 40, 727–736.

    Article  CAS  PubMed  Google Scholar 

  • Haidar, M., Latre de Late, P., Kennedy, E. J., & Langsley, G. (2017). Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria-transformed leukocytes. Bioorganic & Medicinal Chemistry.

    Google Scholar 

  • Heffernan, C., Sumer, H., Guillemin, G. J., Manuelpillai, U., & Verma, P. J. (2012). Design and screening of a glial cell-specific, cell penetrating peptide for therapeutic applications in multiple sclerosis. PLoS ONE, 7, e45501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howl, J., Howl, L., & Jones, S. (2018). The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14. Peptides, 101, 95–105.

    Article  CAS  PubMed  Google Scholar 

  • Howl, J., & Jones, S. (2015). Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells. Journal of Controlled Release: Official journal of the Controlled Release Society, 202, 108–117.

    Article  CAS  Google Scholar 

  • Hsu, T., & Mitragotri, S. (2011). Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer. Proceedings of the National Academy of Sciences of the United States of America, 108, 15816–15821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu, Q., Chen, R., Teesalu, T., Ruoslahti, E., & Clegg, D. O. (2014). Reprogramming human retinal pigmented epithelial cells to neurons using recombinant proteins. Stem Cells Translational Medicine, 3, 1526–1534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, Y. H., Chaousis, S., Cheneval, O., Craik, D. J., & Henriques, S. T. (2015). Optimization of the cyclotide framework to improve cell penetration properties. Frontiers in Pharmacology, 6, 17.

    PubMed  PubMed Central  Google Scholar 

  • Huang, Y., Li, X., Sha, H., Zhang, L., Bian, X., Han, X., et al. (2017). Tumor-penetrating peptide fused to a pro-apoptotic peptide facilitates effective gastric cancer therapy. Oncology Reports, 37, 2063–2070.

    Article  CAS  PubMed  Google Scholar 

  • Hunt, H., Simon-Gracia, L., Tobi, A., Kotamraju, V. R., Sharma, S., Nigul, M., et al. (2017). Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles. Journal of Controlled Release: Official Journal of the Controlled Release Society, 260, 142–153.

    Article  CAS  Google Scholar 

  • Hyvonen, M., Enbäck, J., Huhtala, T., Lammi, J., Sihto, H., Weisell, J., et al. (2014). Novel target for peptide-based imaging and treatment of brain tumors. Molecular Cancer Therapeutics, 13, 996–1007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Im, J., Das, S., Jeong, D., Kim, C. J., Lim, H. S., Kim, K. H., et al. (2017). Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier. International Journal of Pharmaceutics, 528, 646–654.

    Article  CAS  PubMed  Google Scholar 

  • Issaeva, N., Friedler, A., Bozko, P., Wiman, K. G., Fersht, A. R., & Selivanova, G. (2003). Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide. Proceedings of the National Academy of Sciences of the United States of America, 100, 13303–13307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivanova, G. D., Arzumanov, A., Abes, R., Yin, H., Wood, M. J., Lebleu, B., et al. (2008). Improved cell-penetrating peptide-PNA conjugates for splicing redirection in HeLa cells and exon skipping in mdx mouse muscle. Nucleic Acids Research, 36, 6418–6428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki, T., Tokuda, Y., Kotake, A., Okada, H., Takeda, S., Kawano, T., et al. (2015). Cellular uptake and in vivo distribution of polyhistidine peptides. Journal of controlled release: Official Journal of the Controlled Release Society, 210, 115–124.

    Article  CAS  Google Scholar 

  • Jafari, M., Xu, W., Pan, R., Sweeting, C. M., Karunaratne, D. N., & Chen, P. (2014). Serum stability and physicochemical characterization of a novel amphipathic peptide C6M1 for siRNA delivery. PLoS ONE, 9, e97797.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jagot-Lacoussiere, L., Kotula, E., Villoutreix, B. O., Bruzzoni-Giovanelli, H., & Poyet, J. L. (2016). A cell-penetrating peptide targeting AAC-11 specifically induces cancer cells death. Cancer Research, 76, 5479–5490.

    Article  CAS  PubMed  Google Scholar 

  • Jain, A., & Chugh, A. (2016). Mitochondrial transit peptide exhibits cell penetration ability and efficiently delivers macromolecules to mitochondria. FEBS Letters, 590, 2896–2905.

    Article  CAS  PubMed  Google Scholar 

  • Jain, A., Yadav, B. K., & Chugh, A. (2015). Marine antimicrobial peptide tachyplesin as an efficient nanocarrier for macromolecule delivery in plant and mammalian cells. The FEBS Journal, 282, 732–745.

    Article  CAS  PubMed  Google Scholar 

  • Jeong, J. H., Kim, K., Lim, D., Jeong, K., Hong, Y., Nguyen, V. H., et al. (2014). Anti-tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium. PLoS ONE, 9, e80050.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Joanne, P., Galanth, C., Goasdoue, N., Nicolas, P., Sagan, S., Lavielle, S., et al. (2009). Lipid reorganization induced by membrane-active peptides probed using differential scanning calorimetry. Biochimica et Biophysica Acta, 1788, 1772–1781.

    Article  CAS  PubMed  Google Scholar 

  • Jobin, M. L., Bonnafous, P., Temsamani, H., Dole, F., Grelard, A., Dufourc, E. J., et al. (2013). The enhanced membrane interaction and perturbation of a cell penetrating peptide in the presence of anionic lipids: Toward an understanding of its selectivity for cancer cells. Biochimica et Biophysica Acta, 1828, 1457–1470.

    Article  CAS  PubMed  Google Scholar 

  • Johansson, H. J., El-Andaloussi, S., Holm, T., Mae, M., Janes, J., Maimets, T., et al. (2008). Characterization of a novel cytotoxic cell-penetrating peptide derived from p14ARF protein. Molecular Therapy, 16, 115–123.

    Article  CAS  PubMed  Google Scholar 

  • Joliot, A., Pernelle, C., Deagostini-Bazin, H., & Prochiantz, A. (1991). Antennapedia homeobox peptide regulates neural morphogenesis. Proceedings of the National Academy of Sciences of the United States of America, 88, 1864–1868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joliot, A., & Prochiantz, A. (2008). Homeoproteins as natural Penetratin cargoes with signaling properties. Advanced Drug Delivery Reviews, 60, 608–613.

    Article  CAS  PubMed  Google Scholar 

  • Jones, S., Farquhar, M., Martin, A., & Howl, J. (2005). Intracellular translocation of the decapeptide carboxyl terminal of Gi3 alpha induces the dual phosphorylation of p42/p44 MAP kinases. Biochimica et Biophysica Acta, 1745, 207–214.

    Article  CAS  PubMed  Google Scholar 

  • Jung, M. R., Shim, I. K., Kim, E. S., Park, Y. J., Yang, Y. I., Lee, S. K., et al. (2011). Controlled release of cell-permeable gene complex from poly(l-lactide) scaffold for enhanced stem cell tissue engineering. Journal of Controlled Release: Official Journal of the Controlled Release Society, 152, 294–302.

    Article  CAS  Google Scholar 

  • Khafagy EL, S., Iwamae, R., Kamei, N., & Takeda-Morishita, M. (2015). Region-dependent role of cell-penetrating peptides in insulin absorption across the rat small intestinal membrane. The AAPS journal, 17, 1427–1437.

    Google Scholar 

  • Kilk, K., Magzoub, M., Pooga, M., Eriksson, L. E., Langel, Ü., & Gräslund, A. (2001). Cellular internalization of a cargo complex with a novel peptide derived from the third helix of the islet-1 homeodomain. Comparison with the penetratin peptide. Bioconjugate Chemistry, 12, 911–916.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S., Hyun, S., Lee, Y., Lee, Y., & Yu, J. (2016a). Nonhemolytic cell-penetrating peptides: Site specific introduction of glutamine and lysine residues into the alpha-Helical peptide causes deletion of its direct membrane disrupting ability but retention of its cell penetrating ability. Biomacromolecules, 17, 3007–3015.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H., Kitamatsu, M., & Ohtsuki, T. (2017). Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage. Bioorganic & Medicinal Chemistry Letters.

    Google Scholar 

  • Kim, Y., Lillo, A. M., Steiniger, S. C., Liu, Y., Ballatore, C., Anichini, A., et al. (2006). Targeting heat shock proteins on cancer cells: Selection, characterization, and cell-penetrating properties of a peptidic GRP78 ligand. Biochemistry, 45, 9434–9444.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H., Seo, E. H., Lee, S. H., & Kim, B. J. (2016a). The telomerase-derived anticancer peptide vaccine GV1001 as an extracellular heat shock protein-mediated cell-penetrating peptide. International Journal of Molecular Sciences, 17.

    Google Scholar 

  • Kimura, S., Kawano, T., & Iwasaki, T. (2017). Short polyhistidine peptides penetrate effectively into Nicotiana tabacum-cultured cells and Saccharomyces cerevisiae cells. Bioscience, Biotechnology, and Biochemistry, 81, 112–118.

    Article  CAS  PubMed  Google Scholar 

  • Kizaka-Kondoh, S., Itasaka, S., Zeng, L., Tanaka, S., Zhao, T., Takahashi, Y., et al. (2009). Selective killing of hypoxia-inducible factor-1-active cells improves survival in a mouse model of invasive and metastatic pancreatic cancer. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 15, 3433–3441.

    Article  CAS  Google Scholar 

  • Kochurani, K. J., Suganya, A. A., Nair, M. G., Louis, J. M., Majumder, A., Kumar, S. K., et al. (2015). Live detection and purification of cells based on the expression of a histone chaperone, HIRA, using a binding peptide. Scientific Reports, 5.

    Google Scholar 

  • Kondo, E., Saito, K., Tashiro, Y., Kamide, K., Uno, S., Furuya, T., et al. (2012). Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems. Nature Communications, 3, 951.

    Article  PubMed  CAS  Google Scholar 

  • Kumar, S., Sahdev, P., Perumal, O., & Tummala, H. (2012). Identification of a novel skin penetration enhancement peptide by phage display peptide library screening. Molecular Pharmaceutics, 9, 1320–1330.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, P., Wu, H., McBride, J. L., Jung, K. E., Kim, M. H., Davidson, B. L., et al. (2007). Transvascular delivery of small interfering RNA to the central nervous system. Nature, 448, 39–43.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, S., Zakrewsky, M., Chen, M., Menegatti, S., Muraski, J. A., & Mitragotri, S. (2015). Peptides as skin penetration enhancers: Mechanisms of action. Journal of controlled release: Official Journal of the Controlled Release Society, 199, 168–178.

    Article  CAS  Google Scholar 

  • Langel, Ü. (2015). Cell penetrating peptides. Methods and protocols. In Methods in molecular biology (2nd ed., p. 1324). New York: Humana Press.

    Google Scholar 

  • Layalle, S., Volovitch, M., Mugat, B., Bonneaud, N., Parmentier, M. L., Prochiantz, A., et al. (2011). Engrailed homeoprotein acts as a signaling molecule in the developing fly. Development, 138, 2315–2323.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J., Kennedy, P., & Waugh, J. M. (2015a). Experiences with CPP-based self assembling peptide systems for topical delivery of botulinum toxin. Methods in Molecular Biology, 2806–4_27.

    Google Scholar 

  • Lee, H. S., Park, C. B., Kim, J. M., Jang, S. A., Park, I. Y., Kim, M. S., et al. (2008). Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Letters, 271, 47–55.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. Y., Suh, J. S., Kim, J. M., Kim, J. H., Park, H. J., Park, Y. J., et al. (2015b). Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity. International Journal of Nanomedicine, 10, 5423–5434.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lehto, T., Castillo Alvarez, A., Gauck, S., Gait, M. J., Coursindel, T., Wood, M. J., et al. (2014). Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells. Nucleic Acids Research, 42, 3207–3217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lemeshko, V. V. (2013). Electrical potentiation of the membrane permeabilization by new peptides with anticancer properties. Biochimica et Biophysica Acta, 1828, 1047–1056.

    Article  CAS  PubMed  Google Scholar 

  • Lewis, H. D., Husain, A., Donnelly, R. J., Barlos, D., Riaz, S., Ginjupalli, K., et al. (2010). Creation of a novel peptide with enhanced nuclear localization in prostate and pancreatic cancer cell lines. BMC Biotechnology, 10, 79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li, S. Y., Cheng, H., Qiu, W. X., Liu, L. H., Chen, S., Hu, Y., et al. (2015). Protease-activable cell-penetrating peptide-protoporphyrin conjugate for targeted photodynamic therapy in vivo. ACS Applied Materials & Interfaces, 7, 28319–28329.

    Article  CAS  Google Scholar 

  • Li, L., Geisler, I., Chmielewski, J., & Cheng, J. X. (2010). Cationic amphiphilic polyproline helix P11LRR targets intracellular mitochondria. Journal of Controlled Release: Official Journal of the Controlled Release Society, 142, 259–266.

    Article  CAS  Google Scholar 

  • Li, W., Nicol, F., & Szoka Jr., F. C. (2004). GALA: A designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Advanced Drug Delivery Reviews, 56, 967–985.

    Google Scholar 

  • Lim, J., Kim, J., Kang, J., & Jo, D. (2014). Partial somatic to stem cell transformations induced by cell-permeable reprogramming factors. Scientific Reports, 4.

    Google Scholar 

  • Lim, S., Kim, W. J., Kim, Y. H., Lee, S., Koo, J. H., Lee, J. A., et al. (2015). dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature Communications, 6, 8244.

    Google Scholar 

  • Lim, K. J., Sung, B. H., Shin, J. R., Lee, Y. W., Kim Da, J., Yang, K. S., et al. (2013). A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells. PloS One, 8, e66084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin, Y. Z., Yao, S. Y., Veach, R. A., Torgerson, T. R., & Hawiger, J. (1995). Inhibition of nuclear translocation of transcription factor NF-kappa B by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence. Journal of Biological Chemistry, 270, 14255–14258.

    Article  CAS  PubMed  Google Scholar 

  • Lin, C., Zhang, X., Chen, H., Bian, Z., Zhang, G., Riaz, M. K., et al. (2018). Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide. Drug Delivery, 25, 256–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindgren, M., Rosenthal-Aizman, K., Saar, K., Eiriksdottir, E., Jiang, Y., Sassian, M., et al. (2006). Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide. Biochemical Pharmacology, 71, 416–425.

    Article  CAS  PubMed  Google Scholar 

  • Liu, M.-J., Chou, J.-C., & Lee, H.-J. (2013a). A gene delivery method mediated by three arginine-rich cell-penetrating peptides in plant cells. Advanced Studies in Biology, 5, 71–88.

    Article  Google Scholar 

  • Liu, M., Guo, Y. M., Wu, Q. F., Yang, J. L., Wang, P., Wang, S. C., et al. (2006). Paramagnetic particles carried by cell-penetrating peptide tracking of bone marrow mesenchymal stem cells, a research in vitro. Biochemical and Biophysical Research Communications, 347, 133–140.

    Article  CAS  PubMed  Google Scholar 

  • Liu, B. R., Huang, Y. W., Aronstam, R. S., & Lee, H. J. (2016a). Identification of a short cell-penetrating peptide from bovine lactoferricin for intracellular delivery of DNA in human A549 cells. PloS One, 11.

    Google Scholar 

  • Liu, Y., Mei, L., Xu, C., Yu, Q., Shi, K., Zhang, L., et al. (2016b). Dual receptor recognizing cell penetrating peptide for selective targeting, efficient intratumoral diffusion and synthesized anti-glioma therapy. Theranostics, 6, 177–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Y., Xia, X., Xu, L., & Wang, Y. (2013b). Design of hybrid beta-hairpin peptides with enhanced cell specificity and potent anti-inflammatory activity. Biomaterials, 34, 237–250.

    Article  CAS  PubMed  Google Scholar 

  • Lo, S. L., & Wang, S. (2012). Evaluation of the use of amphipathic peptide-based protein carrier for in vitro cancer research. Biochemical and Biophysical Research Communications, 419, 170–174.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Garcia, B., Perez-Paya, E., & Marcos, J. F. (2002). Identification of novel hexapeptides bioactive against phytopathogenic fungi through screening of a synthetic peptide combinatorial library. Applied and Environmental Microbiology, 68, 2453–2460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lundberg, P., el Andaloussi, S., Sutlu, T., Johansson, H., & Langel, Ü. (2007). Delivery of short interfering RNA using endosomolytic cell-penetrating peptides. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 21, 2664–2671.

    Article  CAS  Google Scholar 

  • Luo, Z., Cao, X. W., Li, C., Wu, M. D., Yang, X. Z., Zhao, J., et al. (2016). The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery. Journal of Peptide Science, 22, 689–699.

    Article  CAS  PubMed  Google Scholar 

  • Luque-Ortega, J. R., Van’t Hof, W., Veerman, E. C., Saugar, J. M., & Rivas, L. (2008). Human antimicrobial peptide histatin 5 is a cell-penetrating peptide targeting mitochondrial ATP synthesis in Leishmania. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 22, 1817–1828.

    Google Scholar 

  • Lv, M., Wang, M., Lu, K., Duan, B., & Zhao, Y. (2017). Non-covalent interaction between CA-TAT and calf thymus DNA: Deciphering the binding mode by in vitro studies. International Journal of Biological Macromolecules.

    Google Scholar 

  • Magzoub, M., Sandgren, S., Lundberg, P., Oglecka, K., Lilja, J., Wittrup, A., et al. (2006). N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis. Biochemical and Biophysical Research Communications, 348, 379–385.

    Article  CAS  PubMed  Google Scholar 

  • Mann, A. P., Scodeller, P., Hussain, S., Braun, G. B., Molder, T., Toome, K., et al. (2017). Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer’s disease. Nature Communications, 8, 1403.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mano, M., Henriques, A., Paiva, A., Prieto, M., Gavilanes, F., Simoes, S., et al. (2007). Interaction of S413-PV cell penetrating peptide with model membranes: Relevance to peptide translocation across biological membranes. Journal of peptide science: An Official Publication of the European Peptide Society, 13, 301–313.

    Article  CAS  Google Scholar 

  • Manosroi, J., Lohcharoenkal, W., Gotz, F., Werner, R. G., Manosroi, W., & Manosroi, A. (2014). Novel application of polioviral capsid: Development of a potent and prolonged oral calcitonin using polioviral binding ligand and Tat peptide. Drug Development and Industrial Pharmacy, 40, 1092–1100.

    Article  CAS  PubMed  Google Scholar 

  • Marinova, Z., Vukojevic, V., Surcheva, S., Yakovleva, T., Cebers, G., Pasikova, N., et al. (2005). Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission. The Journal of biological chemistry, 280, 26360–26370.

    Article  CAS  PubMed  Google Scholar 

  • Marks, J. R., Placone, J., Hristova, K., & Wimley, W. C. (2011). Spontaneous membrane-translocating peptides by orthogonal high-throughput screening. Journal of the American Chemical Society, 133, 8995–9004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin, I., Teixido, M., & Giralt, E. (2011). Design, synthesis and characterization of a new anionic cell-penetrating peptide: SAP(E). ChemBioChem, 12, 896–903.

    Article  CAS  PubMed  Google Scholar 

  • McCarthy, H. O., McCaffrey, J., McCrudden, C. M., Zholobenko, A., Ali, A. A., McBride, J. W., et al. (2014). Development and characterization of self-assembling nanoparticles using a bio-inspired amphipathic peptide for gene delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society, 189, 141–149.

    Article  CAS  Google Scholar 

  • McCusker, C. T., Wang, Y., Shan, J., Kinyanjui, M. W., Villeneuve, A., Michael, H., et al. (2007). Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominant-negative STAT-6 peptide. Journal of Immunology, 179, 2556–2564.

    Article  CAS  Google Scholar 

  • Miao, J., Guo, H., Chen, F., Zhao, L., He, L., Ou, Y., et al. (2016). Antibacterial effects of a cell-penetrating peptide isolated from kefir. Journal of Agriculture and Food Chemistry, 22, 22.

    Google Scholar 

  • Milosavljevic, V., Haddad, Y., Merlos Rodrigo, M. A., Moulick, A., Polanska, H., Hynek, D., et al. (2016). The Zinc-Schiff base-Novicidin complex as a potential prostate cancer therapy. PLoS One, 11, e0163983.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mitchell, D. J., Kim, D. T., Steinman, L., Fathman, C. G., & Rothbard, J. B. (2000). Polyarginine enters cells more efficiently than other polycationic homopolymers. Journal of Peptide Research, 56, 318–325.

    Article  CAS  Google Scholar 

  • Montrose, K., Yang, Y., & Krissansen, G. W. (2014). The tetrapeptide core of the carrier peptide Xentry is cell-penetrating: Novel activatable forms of Xentry. Scientific Reports, 4, 4900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morris, M. C., Vidal, P., Chaloin, L., Heitz, F., & Divita, G. (1997). A new peptide vector for efficient delivery of oligonucleotides into mammalian cells. Nucleic Acids Research, 25, 2730–2736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moulay, G., Leborgne, C., Mason, A. J., Aisenbrey, C., Kichler, A., & Bechinger, B. (2017). Histidine-rich designer peptides of the LAH4 family promote cell delivery of a multitude of cargo. Journal of Peptide Science, 23, 320–328.

    Article  CAS  PubMed  Google Scholar 

  • Mousli, M., Bueb, J. L., Bronner, C., Rouot, B., & Landry, Y. (1990). G protein activation: A receptor-independent mode of action for cationic amphiphilic neuropeptides and venom peptides [see comments]. Trends in Pharmacological Sciences, 11, 358–362.

    Article  CAS  PubMed  Google Scholar 

  • Murayama, T., Pujals, S., Hirose, H., Nakase, I., & Futaki, S. (2016). Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N-terminal helix derived from adenovirus internal protein VI as a model. Biopolymers, 106, 430–439.

    Article  CAS  PubMed  Google Scholar 

  • Nakayama, F., Yasuda, T., Umeda, S., Asada, M., Imamura, T., Meineke, V., et al. (2011). Fibroblast growth factor-12 (FGF12) translocation into intestinal epithelial cells is dependent on a novel cell-penetrating peptide domain: Involvement of internalization in the in vivo role of exogenous FGF12. The Journal of Biological Chemistry, 286, 25823–25834.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nasrolahi Shirazi, A., Tiwari, R., Chhikara, B. S., Mandal, D., & Parang, K. (2013). Design and biological evaluation of cell-penetrating peptide-doxorubicin conjugates as prodrugs. Molecular Pharmaceutics, 10, 488–499.

    Google Scholar 

  • Neves-Coelho, S., Eleuterio, R. P., Enguita, F. J., Neves, V., & Castanho, M. (2017). A new noncanonical anionic peptide that translocates a cellular blood-brain barrier model. Molecules, 22.

    Google Scholar 

  • Nguyen, J., Xie, X., Neu, M., Dumitrascu, R., Reul, R., Sitterberg, J., et al. (2008). Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. The Journal of Gene Medicine, 10, 1236–1246.

    Article  CAS  PubMed  Google Scholar 

  • Niesner, U., Halin, C., Lozzi, L., Günthert, M., Neri, P., Wunderli-Allenspach, H., et al. (2002). Quantitation of the tumor-targeting properties of antibody fragments conjugated to cell-permeating HIV-1 TAT peptides. Bioconjugate Chemistry, 13, 729–736.

    Article  CAS  PubMed  Google Scholar 

  • Oehlke, J., Birth, P., Klauschenz, E., Wiesner, B., Beyermann, M., Oksche, A., et al. (2002). Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides. European Journal of Biochemistry, 269, 4025–4032.

    Article  CAS  PubMed  Google Scholar 

  • Oehlke, J., Krause, E., Wiesner, B., Beyermann, M., & Bienert, M. (1997). Extensive cellular uptake into endothelial cells of an amphipathic beta-sheet forming peptide. FEBS Letters, 415, 196–199.

    Article  CAS  PubMed  Google Scholar 

  • Oehlke, J., Scheller, A., Wiesner, B., Krause, E., Beyermann, M., Klauschenz, E., et al. (1998). Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically. Biochimica et Biophysica Acta, 1414, 127–139.

    Article  CAS  PubMed  Google Scholar 

  • Okitsu, K., Misawa, T., Shoda, T., Kurihara, M., & Demizu, Y. (2017). Development of an ON/OFF switchable fluorescent probe targeting His tag fused proteins in living cells. Bioorganic & Medicinal Chemistry Letters, 27, 3417–3422.

    Article  CAS  Google Scholar 

  • Oren, Z., Lerman, J. C., Gudmundsson, G. H., Agerberth, B., & Shai, Y. (1999). Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: Relevance to the molecular basis for its non-cell-selective activity. The Biochemical Journal, 341, 501–513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orihuela, C. J., Mahdavi, J., Thornton, J., Mann, B., Wooldridge, K. G., Abouseada, N., et al. (2009). Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. The Journal of Clinical Investigation, 119, 1638–1646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Östlund, P., Kilk, K., Lindgren, M., Hällbrink, M., Jiang, Y., Budihna, M., et al. (2005). Cell-penetrating mimics of agonist-activated G-protein coupled receptors. International Journal of Peptide Research and Therapeutics, 11, 237–247.

    Article  CAS  Google Scholar 

  • Otvos Jr., L., Bokonyi, K., Varga, I., Otvos, B. I., Hoffmann, R., Ertl, H. C., et al. (2000). Insect peptides with improved protease-resistance protect mice against bacterial infection. Protein Science: A Publication of the Protein Society, 9, 742–749.

    Article  Google Scholar 

  • Paasonen, L., Sharma, S., Braun, G. B., Kotamraju, V. R., Chung, T. D., She, Z. G., et al. (2016). New p32/gC1qR ligands for targeted tumor drug delivery. Chembiochem: A European Journal of Chemical Biology, 17, 570–575.

    Article  CAS  PubMed  Google Scholar 

  • Pan, R., Xu, W., Ding, Y., Lu, S., & Chen, P. (2016). Uptake mechanism and direct translocation of a new CPP for siRNA delivery. Molecular Pharmaceutics, 23, 23.

    Google Scholar 

  • Paolella, G., Lepretti, M., Martucciello, S., Nanayakkara, M., Auricchio, S., Esposito, C., et al. (2018). The toxic alpha-gliadin peptide 31–43 enters cells without a surface membrane receptor. Cell Biology International, 42, 112–120.

    Article  CAS  PubMed  Google Scholar 

  • Park, C. B., Kim, H. S., & Kim, S. C. (1998). Mechanism of action of the antimicrobial peptide buforin II: Buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochemical and Biophysical Research Communications, 244, 253–257.

    Article  CAS  PubMed  Google Scholar 

  • Patel, R. R., Sundin, G. W., Yang, C. H., Wang, J., Huntley, R. B., Yuan, X., et al. (2017). Exploration of using antisense peptide nucleic acid (PNA)-cell penetrating peptide (CPP) as a novel bactericide against fire blight pathogen Erwinia amylovora. Frontiers in Microbiology, 8, 687.

    PubMed  PubMed Central  Google Scholar 

  • Peng, S., Barba-Bon, A., Pan, Y. C., Nau, W. M., Guo, D. S., & Hennig, A. (2017a). Phosphorylation-responsive membrane transport of peptides. Angewandte Chemie (International ed. in English), 56, 15742–15745.

    Article  CAS  Google Scholar 

  • Peng, Z. H., & Kopecek, J. (2015). Enhancing accumulation and penetration of HPMA copolymer-doxorubicin conjugates in 2D and 3D prostate cancer cells via iRGD conjugation with an MMP-2 cleavable spacer. Journal of the American Chemical Society, 137, 6726–6729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng, J., Rao, Y., Yang, X., Jia, J., Wu, Y., Lu, J., et al. (2017b). Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate. Neuroscience Letters, 650, 153–160.

    Article  CAS  PubMed  Google Scholar 

  • Percipalle, P., Fomproix, N., Kylberg, K., Miralles, F., Bjorkroth, B., Daneholt, B., et al. (2003). An actin-ribonucleoprotein interaction is involved in transcription by RNA polymerase II. Proceedings of the National Academy of Sciences of the United States of America, 100, 6475–6480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perera, Y., Costales, H. C., Diaz, Y., Reyes, O., Farina, H. G., Mendez, L., et al. (2012). Sensitivity of tumor cells towards CIGB-300 anticancer peptide relies on its nucleolar localization. Journal of peptide science: An Official Publication of the European Peptide Society, 18, 215–223.

    Article  CAS  Google Scholar 

  • Pichon, C., Freulon, I., Midoux, P., Mayer, R., Monsigny, M., & Roche, A. C. (1997). Cytosolic and nuclear delivery of oligonucleotides mediated by an amphiphilic anionic peptide. Antisense and Nucleic Acid Drug Development, 7, 335–343.

    Article  CAS  PubMed  Google Scholar 

  • Poillot, C., Dridi, K., Bichraoui, H., Pecher, J., Alphonse, S., Douzi, B., et al. (2010). D-Maurocalcine, a pharmacologically inert efficient cell-penetrating peptide analogue. The Journal of Biological Chemistry, 285, 34168–34180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ponnappan, N., Budagavi, D. P., & Chugh, A. (2017). CyLoP-1: Membrane-active peptide with cell-penetrating and antimicrobial properties. Biochimica et Biophysica Acta, 1859, 167–176.

    Article  CAS  PubMed  Google Scholar 

  • Ponnappan, N., & Chugh, A. (2017). Cell-penetrating and cargo-delivery ability of a spider toxin-derived peptide in mammalian cells. European Journal of Pharmaceutics and Biopharmaceutics, 114, 145–153.

    Article  CAS  PubMed  Google Scholar 

  • Pooga, M., Hällbrink, M., Zorko, M., & Langel, Ü. (1998). Cell penetration by transportan. FASEB Journal, 12, 67–77.

    Article  CAS  PubMed  Google Scholar 

  • Prochiantz, A., Fuchs, J., & di Nardo, A. A. (2014). Postnatal signalling with homeoprotein transcription factors. Philosophical Transactions of the Royal Society B: Biological Sciences, 369.

    Google Scholar 

  • Pujals, S., Fernandez-Carneado, J., Lopez-Iglesias, C., Kogan, M. J., & Giralt, E. (2006). Mechanistic aspects of CPP-mediated intracellular drug delivery: Relevance of CPP self-assembly. Biochimica et Biophysica Acta, 1758, 264–279.

    Article  CAS  PubMed  Google Scholar 

  • Pujals, S., Sabido, E., Tarrago, T., & Giralt, E. (2007). all-D proline-rich cell-penetrating peptides: A preliminary in vivo internalization study. Biochemical Society Transactions, 35, 794–796.

    Article  CAS  PubMed  Google Scholar 

  • Pushpanathan, M., Gunasekaran, P., & Rajendhran, J. (2013). Mechanisms of the antifungal action of marine metagenome-derived peptide, MMGP1, against Candida albicans. PloS One, 8.

    Google Scholar 

  • Qi, X., Droste, T., & Kao, C. C. (2011). Cell-penetrating peptides derived from viral capsid proteins. Molecular Plant-Microbe Interactions: MPMI, 24, 25–36.

    Article  CAS  PubMed  Google Scholar 

  • Qian, Z., Larochelle, J. R., Jiang, B., Lian, W., Hard, R. L., Selner, N. G., et al. (2014). Early endosomal escape of a cyclic cell-penetrating peptide allows effective cytosolic cargo delivery. Biochemistry, 53, 4034–4046.

    Article  CAS  PubMed  Google Scholar 

  • Qifan, W., Fen, N., Ying, X., Xinwei, F., Jun, D., & Ge, Z. (2016). iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine, 11, 11.

    Google Scholar 

  • Rakowska, P. D., Lamarre, B., & Ryadnov, M. G. (2014). Probing label-free intracellular quantification of free peptide by MALDI-ToF mass spectrometry. Methods, 68, 331–337.

    Article  CAS  PubMed  Google Scholar 

  • Ramakrishna, S., Kwaku Dad, A. B., Beloor, J., Gopalappa, R., Lee, S. K. & Kim, H. (2014). Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA. Genome Research, 24, 1020–1027.

    Google Scholar 

  • Rassu, G., Soddu, E., Posadino, A. M., Pintus, G., Sarmento, B., Giunchedi, P., et al. (2017). Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy. Colloids and Surfaces. B, Biointerfaces, 152, 296–301.

    Article  CAS  PubMed  Google Scholar 

  • Repke, H., & Bienert, M. (1987). Mast cell activation—A receptor-independent mode of substance P action? FEBS Letters, 221, 236–240.

    Article  CAS  PubMed  Google Scholar 

  • Reyes-Cortes, R., Acosta-Smith, E., Mondragon-Flores, R., Nazmi, K., Bolscher, J. G., Canizalez-Roman, A., et al. (2017). Antibacterial and cell penetrating effects of LFcin17-30, LFampin265-284, and LF chimera on enteroaggregative Escherichia coli. Biochemistry and Cell Biology, 95, 76–81.

    Article  CAS  PubMed  Google Scholar 

  • Rhee, M., & Davis, P. (2006). Mechanism of uptake of C105Y, a novel cell-penetrating peptide. The Journal of Biological Chemistry, 281, 1233–1240.

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues, M., Santos, A., de la Torre, B. G., Radis-Baptista, G., Andreu, D., & Santos, N. C. (2012). Molecular characterization of the interaction of crotamine-derived nucleolar targeting peptides with lipid membranes. Biochimica et Biophysica Acta, 1818, 2707–2717.

    Article  CAS  PubMed  Google Scholar 

  • Rojas, M., Donahue, J. P., Tan, Z., & Lin, Y. Z. (1998). Genetic engineering of proteins with cell membrane permeability. Nature Biotechnology, 16, 370–375.

    Article  CAS  PubMed  Google Scholar 

  • Rosenbluh, J., Singh, S. K., Gafni, Y., Graessmann, A., & Loyter, A. (2004). Non-endocytic penetration of core histones into petunia protoplasts and cultured cells: A novel mechanism for the introduction of macromolecules into plant cells. Biochimica et Biophysica Acta, 1664, 230–240.

    Article  CAS  PubMed  Google Scholar 

  • Rousselle, C., Clair, P., Lefauconnier, J. M., Kaczorek, M., Scherrmann, J. M., & Temsamani, J. (2000). New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Molecular Pharmacology, 57, 679–686.

    Article  CAS  PubMed  Google Scholar 

  • Rownicki, M., Wojciechowska, M., Wierzba, A. J., Czarnecki, J., Bartosik, D., Gryko, D., et al. (2017). Vitamin B12 as a carrier of peptide nucleic acid (PNA) into bacterial cells. Scientific Report, 7, 7644.

    Article  CAS  Google Scholar 

  • Rydberg, H. A., Carlsson, N., & Norden, B. (2012). Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function. Biochemical and Biophysical Research Communications, 427, 261–265.

    Article  CAS  PubMed  Google Scholar 

  • Sadler, K., Eom, K. D., Yang, J. L., Dimitrova, Y., & Tam, J. P. (2002). Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7. Biochemistry, 41, 14150–14157.

    Article  CAS  PubMed  Google Scholar 

  • Saleh, A. F., Arzumanov, A., Abes, R., Owen, D., Lebleu, B., & Gait, M. J. (2010). Synthesis and splice-redirecting activity of branched, arginine-rich peptide dendrimer conjugates of peptide nucleic acid oligonucleotides. Bioconjugate Chemistry, 21, 1902–1911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samuels, S., Alwan, Z., Egnin, M., Jaynes, J., Connell, T. D., Bernard, G. C., et al. (2017). Novel therapeutic approach for inhibition of HIV-1 Using cell-penetrating peptide and bacterial toxins. Journal of AIDS and Clinical Research, 8.

    Google Scholar 

  • Sangtani, A., Petryayeva, E., Wu, M., Susumu, K., Oh, E., Huston, A. L., et al. (2018). Intracellularly actuated quantum dot-peptide-doxorubicin nanobioconjugates for controlled drug delivery via the endocytic pathway. Bioconjugate Chemistry, 29, 136–148.

    Article  CAS  PubMed  Google Scholar 

  • Sasaki, Y., Minamizawa, M., Ambo, A., Sugawara, S., Ogawa, Y., & Nitta, K. (2008). Cell-penetrating peptide-conjugated XIAP-inhibitory cyclic hexapeptides enter into Jurkat cells and inhibit cell proliferation. FEBS Journal, 275, 6011–6021.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt, S., Adjobo-Hermans, M. J., Kohze, R., Enderle, T., Brock, R., & Milletti, F. (2017). Identification of short hydrophobic cell-penetrating peptides for cytosolic peptide delivery by rational design. Bioconjugate Chemistry, 28, 382–389.

    Article  CAS  PubMed  Google Scholar 

  • Sciani, J. M., Vigerelli, H., Costa, A. S., Camara, D. A., Junior, P. L., & Pimenta, D. C. (2017). An unexpected cell-penetrating peptide from Bothrops jararaca venom identified through a novel size exclusion chromatography screening. Journal of Peptide Science, 23, 68–76.

    Article  CAS  PubMed  Google Scholar 

  • Serna, N., Sanchez-Garcia, L., Sanchez-Chardi, A., Unzueta, U., Roldan, M., Mangues, R., et al. (2017). Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity. Acta Biomaterialia, 60, 256–263.

    Article  CAS  PubMed  Google Scholar 

  • Shabanpoor, F., Hammond, S. M., Abendroth, F., Hazell, G., Wood, M. J. A., & Gait, M. J. (2017). Identification of a peptide for systemic brain delivery of a morpholino oligonucleotide in mouse models of spinal muscular atrophy. Nucleic Acid Therapeutics, 27, 130–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, T. H., Sung, E. S., Kim, Y. J., Kim, K. S., Kim, S. H., Kim, S. K., et al. (2014). Enhancement of the tumor penetration of monoclonal antibody by fusion of a neuropilin-targeting peptide improves the antitumor efficacy. Molecular Cancer Therapeutics, 13, 651–661.

    Article  CAS  PubMed  Google Scholar 

  • Shteinfer-Kuzmine, A., Arif, T., Krelin, Y., Tripathi, S. S., Paul, A., & Shoshan-Barmatz, V. (2017). Mitochondrial VDAC1-based peptides: Attacking oncogenic properties in glioblastoma. Oncotarget, 8, 31329–31346.

    Article  PubMed  PubMed Central  Google Scholar 

  • Signorelli, S., Santini, S., Yamada, T., Bizzarri, A. R., Beattie, C. W., & Cannistraro, S. (2017). Binding of amphipathic cell penetrating peptide p28 to wild type and mutated p53 as studied by Raman, Atomic Force and Surface Plasmon Resonance spectroscopies. Biochimica et Biophysica Acta, 1861, 910–921.

    Article  CAS  PubMed  Google Scholar 

  • Smilansky, A., Dangoor, L., Nakdimon, I., Ben-Hail, D., Mizrachi, D., & Shoshan-Barmatz, V. (2015). The voltage-dependent anion channel 1 mediates amyloid beta toxicity and represents a potential target for Alzheimer Disease therapy. The Journal of biological chemistry, 290, 30670–30683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soler, M., Gonzalez-Bartulos, M., Soriano-Castell, D., Ribas, X., Costas, M., Tebar, F., et al. (2014). Identification of BP16 as a non-toxic cell-penetrating peptide with highly efficient drug delivery properties. Organic & Biomolecular Chemistry, 12, 1652–1663.

    Article  CAS  Google Scholar 

  • Song, L., Sun, Z. Y., Coleman, K. E., Zwick, M. B., Gach, J. S., Wang, J. H., et al. (2009). Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proceedings of the National Academy of Sciences of the United States of America, 106, 9057–9062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soomets, U., Lindgren, M., Gallet, X., Hällbrink, M., Elmquist, A., Balaspiri, L., et al. (2000). Deletion analogues of transportan. Biochimica et Biophysica Acta, 1467, 165–176.

    Article  CAS  PubMed  Google Scholar 

  • Soudah, T., Mogilevsky, M., Karni, R., & Yavin, E. (2017). CLIP6-PNA-peptide conjugates: Non-endosomal delivery of splice switching oligonucleotides. Bioconjugate Chemistry, 28, 3036–3042.

    Article  CAS  PubMed  Google Scholar 

  • Speltz, T. E., Danes, J. M., Stender, J. D., Frasor, J., & Moore, T. W. (2018). A cell-permeable stapled peptide inhibitor of the estrogen receptor/coactivator interaction. ACS Chemical Biology.

    Google Scholar 

  • Sun, P., Huang, W., Kang, L., Jin, M., Fan, B., Jin, H., et al. (2017). siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis. International Journal of Nanomedicine, 12, 3221–3234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki, S., Itakura, S., Matsui, R., Nakayama, K., Nishi, T., Nishimoto, A., et al. (2017). Tumor microenvironment-sensitive liposomes penetrate tumor tissue via attenuated interaction of the extracellular matrix and tumor cells and accompanying actin depolymerization. Biomacromolecules, 18, 535–543.

    Article  CAS  PubMed  Google Scholar 

  • Tacken, P. J., Joosten, B., Reddy, A., Wu, D., Eek, A., Laverman, P., et al. (2008). No advantage of cell-penetrating peptides over receptor-specific antibodies in targeting antigen to human dendritic cells for cross-presentation. Journal of Immunology, 180, 7687–7696.

    Article  CAS  Google Scholar 

  • Tailhades, J., Takizawa, H., Gait, M. J., Wellings, D. A., Wade, J. D., Aoki, Y., et al. (2017). Solid-phase synthesis of difficult purine-rich PNAs through selective Hmb incorporation: Application to the total synthesis of cell penetrating peptide-PNAs. Frontiers in Chemistry, 5, 81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tajik-Ahmadabad, B., Polyzos, A., Separovic, F., & Shabanpoor, F. (2017). Amphiphilic lipopeptide significantly enhances uptake of charge-neutral splice switching morpholino oligonucleotide in spinal muscular atrophy patient-derived fibroblasts. International Journal of Pharmaceutics, 532, 21–28.

    Article  CAS  PubMed  Google Scholar 

  • Tan, H., Huang, Y., Xu, J., Chen, B., Zhang, P., Ye, Z., et al. (2017). Spider toxin peptide lycosin-I functionalized gold nanoparticles for in vivo tumor targeting and therapy. Theranostics, 7, 3168–3178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan, M., Lan, K. H., Yao, J., Lu, C. H., Sun, M., Neal, C. L., et al. (2006). Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT-based ErbB2-targeting signal transducers and activators of transcription 3-blocking peptide. Cancer Research, 66, 3764–3772.

    Article  CAS  PubMed  Google Scholar 

  • Taylor, B. N., Mehta, R. R., Yamada, T., Lekmine, F., Christov, K., Chakrabarty, A. M. (2009). Noncationic peptides obtained from azurin preferentially enter cancer cells. Cancer Research, 69, 537–546.

    Article  CAS  PubMed  Google Scholar 

  • Tchoumi Neree, A., Nguyen, P. T., Chatenet, D., Fournier, A., & Bourgault, S. (2014). Secondary conformational conversion is involved in glycosaminoglycans-mediated cellular uptake of the cationic cell-penetrating peptide PACAP. FEBS Letters, 588, 4590–4596.

    Google Scholar 

  • Toba, M., Alzoubi, A., O’Neill, K., Abe, K., Urakami, T., Komatsu, M., et al. (2014). A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension. American Journal of Pathology, 184, 369–375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Torgerson, T. R., Colosia, A. D., Donahue, J. P., Lin, Y. Z., & Hawiger, J. (1998). Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. Journal of Immunology, 161, 6084–6092.

    CAS  Google Scholar 

  • Tuttolomondo, M., Casella, C., Hansen, P. L., Polo, E., Herda, L. M., Dawson, K. A., et al. (2017). Human DMBT1-derived cell-penetrating peptides for intracellular siRNA delivery. Molecular Therapy—Nucleic Acids, 8, 264–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valeur, E., Knerr, L., Olwegard-Halvarsson, M., & Lemurell, M. (2017). Targeted delivery for regenerative medicines: An untapped opportunity for drug conjugates. Drug Discov Today, 22, 841–847.

    Article  CAS  PubMed  Google Scholar 

  • Vij, M., Natarajan, P., Pattnaik, B. R., Alam, S., Gupta, N., Santhiya, D., et al. (2016a). Non-invasive topical delivery of plasmid DNA to the skin using a peptide carrier. Journal of Controlled Release: Official Journal of the Controlled Release Society, 222, 159–168.

    Article  CAS  Google Scholar 

  • Vij, M., Natarajan, P., Yadav, A. K., Patil, K. M., Pandey, T., Gupta, N., et al. (2016b). Efficient cellular entry of (r-x-r)-type carbamate-plasmid DNA complexes and its implication for noninvasive topical DNA delivery to skin. Molecular Pharmaceutics, 13, 1779–1790.

    Article  CAS  PubMed  Google Scholar 

  • Villa-Cedillo, S. A., Rodriguez-Rocha, H., Zavala-Flores, L. M., Montes-De-oca-luna, R., Garcia-Garcia, A., Loera-Arias, M. J., et al. (2017). Asn194Lys mutation in RVG29 peptide increases GFP transgene delivery by endocytosis to neuroblastoma and astrocyte cells. Journal of Pharmacy and Pharmacology, 69, 1352–1363.

    Article  CAS  PubMed  Google Scholar 

  • Vives, E., Brodin, P., & Lebleu, B. (1997a). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. Journal of Biological Chemistry, 272, 16010–16017.

    Article  CAS  PubMed  Google Scholar 

  • Vives, E., Brodin, P., & Lebleu, B. (1997b). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. The Journal of Biological Xhemistry, 272, 16010–16017.

    Article  CAS  Google Scholar 

  • Wada, S. I., Takesada, A., Nagamura, Y., Sogabe, E., Ohki, R., Hayashi, J., et al. (2017). Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery. Bioorganic & Medicinal Chemistry Letters, 27, 5378–5381.

    Article  CAS  Google Scholar 

  • Wahlmuller, F. C., Yang, H., Furtmuller, M., & Geiger, M. (2017). Regulation of the extracellular SERPINA5 (Protein C Inhibitor) penetration through cellular membranes. Advances in Experimental Medicine and Biology, 966, 93–101.

    Article  PubMed  CAS  Google Scholar 

  • Waldmann, H., Valeur, E., Gueret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., et al. (2017). New modalities for challenging targets in drug discovery. Angewandte Chemie, 56, 10294–10323.

    Article  PubMed  CAS  Google Scholar 

  • Wang, X., Qiu, Y., Yu, Q., Li, H., Chen, X., Li, M., et al. (2017). Enhanced glioma therapy by synergistic inhibition of autophagy and tyrosine kinase activity. International Journal of Pharmaceutics, 536, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y. F., Xu, X., Fan, X., Zhang, C., Wei, Q., Wang, X., et al. (2011). A cell-penetrating peptide suppresses inflammation by inhibiting NF-kappaB signaling. Molecular Therapy: The journal of the American Society of Gene Therapy, 19, 1849–1857.

    Article  CAS  Google Scholar 

  • Watson, G. M., Kulkarni, K., Brandt, R., del Borgo, M. P., Aguilar, M. I., & Wilce, J. A. (2017). shortened penetratin cell-penetrating peptide is insufficient for cytosolic delivery of a Grb7 targeting peptide. ACS Omega, 2, 670–677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wender, P. A., Jessop, T. C., Pattabiraman, K., Pelkey, E. T., & Vandeusen, C. L. (2001). An efficient, scalable synthesis of the molecular transporter octaarginine via a segment doubling strategy. Organic Letters, 3, 3229–3232.

    Article  CAS  PubMed  Google Scholar 

  • Wimley, W. C., & White, S. H. (2000). Determining the membrane topology of peptides by fluorescence quenching. Biochemistry, 39, 161–170.

    Article  CAS  PubMed  Google Scholar 

  • Woldetsadik, A. D., Vogel, M. C., Rabeh, W. M., & Magzoub, M. (2017). Hexokinase II-derived cell-penetrating peptide targets mitochondria and triggers apoptosis in cancer cells. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 9.

    Google Scholar 

  • Wongso, D., Dong, J., Ueda, H., & Kitaguchi, T. (2017). Flashbody: A next generation fluobody with fluorescence intensity enhanced by antigen binding. Analytical Chemistry, 89, 6719–6725.

    Article  CAS  PubMed  Google Scholar 

  • Wyman, T. B., Nicol, F., Zelphati, O., Scaria, P. V., Plank, C., & Szoka Jr., F. C. (1997). Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers. Biochemistry, 36, 3008–3017.

    Google Scholar 

  • Xiao, Y., Zhang, E., & Fu, A. (2017). Promotion of SH-SY5Y cell growth by gold nanoparticles modified with 6-mercaptopurine and a neuron-penetrating peptide. Nanoscale Research Letters, 12, 641.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamada, T., Das Gupta, T. K., & Beattie, C. W. (2016). p 28-mediated activation of p53 in G2/M phase of the cell cycle enhances the efficacy of DNA damaging and antimitotic chemotherapy. Cancer Research, 26.

    Google Scholar 

  • Yanez, R. J. R., Lamprecht, R., Granadillo, M., Weber, B., Torrens, I., Rybicki, E. P., et al. (2017). Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in Nicotiana benthamiana. PLoS One, 12, e0183177.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang, J., Li, Q., Yang, X., Feng, Y., Ren, X., Shi, C., et al. (2016). Multitargeting Gene delivery systems for enhancing the transfection of endothelial cells. Macromolecular Rapid Communications, 37, 1926–1931.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J., Tsutsumi, H., Furuta, T., Sakurai, M., & Mihara, H. (2014). Interaction of amphiphilic alpha-helical cell-penetrating peptides with heparan sulfate. Organic & Biomolecular Chemistry, 12, 4673–4681.

    Article  CAS  Google Scholar 

  • Yao, H., Wang, K., Wang, Y., Wang, S., Li, J., Lou, J., et al. (2015). Enhanced blood-brain barrier penetration and glioma therapy mediated by a new peptide modified gene delivery system. Biomaterials, 37, 345–352.

    Article  CAS  PubMed  Google Scholar 

  • Yoneda, Y., Semba, T., Kaneda, Y., Noble, R. L., Matsuoka, Y., Kurihara, T., et al. (1992). A long synthetic peptide containing a nuclear localization signal and its flanking sequences of SV40 T-antigen directs the transport of IgM into the nucleus efficiently. Experimental Cell Research, 201, 313–320.

    Article  CAS  PubMed  Google Scholar 

  • Yu, J., Sun, L., Zhou, J., Gao, L., Nan, L., Zhao, S., et al. (2017). Self-assembled tumor-penetrating peptide-modified poly(l-gamma-glutamylglutamine)-paclitaxel nanoparticles based on hydrophobic interaction for the treatment of glioblastoma. Bioconjugate Chemistry, 28, 2823–2831.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, L., Zhang, Y., Tai, L., Jiang, K., Xie, C., Li, Z., et al. (2016). Functionalized cell nucleus-penetrating peptide combined with doxorubicin for synergistic treatment of glioma. Acta Biomaterialia, 42, 90–101.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, H., Zhao, Q., Bhattacharya, S., Waheed, A. A., Tong, X., Hong, A., et al. (2008). A cell-penetrating helical peptide as a potential HIV-1 inhibitor. Journal of Molecular Biology, 378, 565–580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, B. Q., Guo, Y. R., Li, X. L., Zang, T., Qu, H. Y., Zhou, J. P., et al. (2011). Amelioration of dementia induced by Abeta 22-35 through rectal delivery of undecapeptide-hEGF to mouse brain. International Journal of Pharmaceutics, 405, 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Y., Lou, D., Burkett, J., & Kohler, H. (2001). Chemical engineering of cell penetrating antibodies. Journal of Immunological Methods, 254, 137–145.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, K., Luo, G., Giannelli, S., & Szeto, H. H. (2005). Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. Biochemical Pharmacology, 70, 1796–1806.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, C., Tong, Y., Li, X., Shao, L., Chen, L., Lu, J., et al. (2018). Photosensitive nanoparticles combining vascular-independent intratumor distribution and on-demand oxygen-depot delivery for enhanced cancer photodynamic therapy. Small.

    Google Scholar 

  • Zhou, N., Wu, J., Qin, Y. Y., Zhao, X. L., Ding, Y., Sun, L. S., et al. (2017). Novel peptide MT23 for potent penetrating and selective targeting in mouse melanoma cancer cells. European Journal of Pharmaceutics and Biopharmaceutics, 120, 80–88.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Stockholms Län, Sweden

    Ülo Langel

  2. Institute of Technology, University of Tartu, Tartu, Estonia

    Ülo Langel

Authors
  1. Ülo Langel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ülo Langel .

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Langel, Ü. (2019). Introduction. In: CPP, Cell-Penetrating Peptides. Springer, Singapore. https://doi.org/10.1007/978-981-13-8747-0_1

Download citation

Publish with us

Policies and ethics

Search

Navigation