Abstract
Artificial oligoamino acids with appropriate protecting groups can be used for the sequential assembly of oligoaminoamides on solid-phase. With the help of these oligoamino acids multifunctional nucleic acid (NA) carriers can be designed and produced in highly defined topologies. Here we describe the synthesis of the artificial oligoamino acid Fmoc-Stp(Boc3)-OH, the subsequent assembly into sequence-defined oligomers and the formulation of tumor-targeted plasmid DNA (pDNA) polyplexes.
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References
Schaffert D, Wagner E (2008) Gene therapy progress and prospects: synthetic polymer-based systems. Gene Ther 15(16):1131–1138
Lächelt U, Kos P, Mickler FM et al (2014) Fine-tuning of proton sponges by precise diaminoethanes and histidines in pDNA polyplexes. Nanomed NBM 1:35–44. doi:10.1016/j.nano.2013.07.008
Lächelt U, Wagner E (2015) Nucleic acid therapeutics using polyplexes: a journey of 50 years (and beyond). Chem Rev. 115(19):11043–11078. doi:10.1021/cr5006793
Ziebarth JD, Wang Y (2010) Understanding the protonation behavior of linear polyethylenimine in solutions through Monte Carlo simulations. Biomacromolecules 11(1):29–38. doi:10.1021/bm900842d
Boussif O, Lezoualc’h F, Zanta MA et al (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 92(16):7297–7301
Behr JP (1997) The proton sponge: a trick to enter cells the viruses did not exploit. Chimia 51(1-2):34–36
Fischer D, Li Y, Ahlemeyer B et al (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24(7):1121–1131
Breunig M, Lungwitz U et al (2007) Breaking up the correlation between efficacy and toxicity for nonviral gene delivery. Proc Natl Acad Sci U S A 104(36):14454–14459. doi:10.1073/pnas.0703882104
Chollet P, Favrot MC et al (2002) Side-effects of a systemic injection of linear polyethylenimine-DNA complexes. J Gene Med 4(1):84–91
Schaffert D, Badgujar N, Wagner E (2011) Novel Fmoc-polyamino acids for solid-phase synthesis of defined polyamidoamines. Org Lett 13(7):1586–1589. doi:10.1021/ol200381z
Schaffert D, Troiber C, Salcher EE et al (2011) Solid-phase synthesis of sequence-defined T-, i-, and U-shape polymers for pDNA and siRNA delivery. Angew Chem Int Ed Engl 50(38):8986–8989. doi:10.1002/anie.201102165
Schaffert D, Troiber C, Wagner E (2012) New sequence-defined polyaminoamides with tailored endosomolytic properties for plasmid DNA delivery. Bioconjug Chem 23(6):1157–1165. doi:10.1021/bc200614x
Scholz C, Kos P, Wagner E (2014) Comb-like oligoaminoethane carriers: change in topology improves pDNA delivery. Bioconjug Chem 25(2):251–261. doi:10.1021/bc400392y
Salcher EE, Kos P, Fröhlich T et al (2012) Sequence-defined four-arm oligo(ethanamino)amides for pDNA and siRNA delivery: Impact of building blocks on efficacy. J Control Release 164(3):380–386. doi:10.1016/j.jconrel.2012.06.023
Martin I, Dohmen C, Mas-Moruno C et al (2012) Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery. Org Biomol Chem 10(16):3258–3268. doi:10.1039/c2ob06907e
Scholz C, Kos P, Leclercq L et al (2014) Correlation of length of linear oligo(ethanamino) amides with gene transfer and cytotoxicity. ChemMedChem 9(9):2104–2110. doi:10.1002/cmdc.201300483
Klein PM, Müller K, Gutmann C et al (2015) Twin disulfides as opportunity for improving stability and transfection efficiency of oligoaminoethane polyplexes. J Control Release 205:109–119. doi:10.1016/j.jconrel.2014.12.035
Leng QX, Mixson AJ (2005) Modified branched peptides with a histidine-rich tail enhance in vitro gene transfection. Nucleic Acids Res 33(4):e40. doi:10.1039/nar/gni040
Midoux P, Monsigny M (1999) Efficient gene transfer by histidylated polylysine/pDNA complexes. Bioconjug Chem 10(3):406–411. doi:10.1021/bc9801070
Hashemi M, Parhiz BH et al (2011) Modified polyethyleneimine with histidine-lysine short peptides as gene carrier. Cancer Gene Ther 18(1):12–19. doi:10.1038/cgt.2010.57
Knop K, Hoogenboom R et al (2010) Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed Engl 49(36):6288–6308. doi:10.1002/anie.200902672
Hatakeyama H, Akita H, Harashima H (2013) The polyethyleneglycol dilemma: advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors. Biol Pharm Bull 36(6):892–899
Boccaccio C, Comoglio PM (2006) Invasive growth: a MET-driven genetic programme for cancer and stem cells. Nat Rev Cancer 6(8):637–645. doi:10.1038/nrc1912
Zhao P, Grabinski T, Gao C et al (2007) Identi-fication of a met-binding peptide from a phage display library. Clin Cancer Res 13(20):6049–6055. doi:10.1158/1078-0432.CCR-07-0035
Kim EM, Park EH, Cheong SJ et al (2009) In vivo imaging of mesenchymal-epithelial transition factor (c-Met) expression using an optical imaging system. Bioconjug Chem 20(7):1299–1306. doi:10.1021/bc8005539
Kos P, Lächelt U, Herrmann A et al (2015) Histidine-rich stabilized polyplexes for cMet-directed tumor-targeted gene transfer. Nanoscale 7(12):5350–5362. doi:10.1039/c4nr06556e
Broda E, Mickler FM, Lächelt U et al (2015) Assessing potential peptide targeting ligands by quantification of cellular adhesion of model nanoparticles under flow conditions. J Control Release 213:79–85. doi:10.1016/j.jconrel.2015.06.030
Kaiser E, Colescott RL et al (1970) Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem 34(2):595–598
Acknowledgements
This work was supported by the German Research Foundation (DFG) Excellence Cluster ″Nanosystems Initiative Munich″ and DFG Collaborative Research Center SFB824. We thank Wolfgang Rödl and Miriam Höhn for technical support, and Olga Brück for skillful assistance.
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Morys, S., Wagner, E., Lächelt, U. (2016). From Artificial Amino Acids to Sequence-Defined Targeted Oligoaminoamides. In: Candiani, G. (eds) Non-Viral Gene Delivery Vectors. Methods in Molecular Biology, vol 1445. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3718-9_15
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DOI: https://doi.org/10.1007/978-1-4939-3718-9_15
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