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PIP–NaCo, a Synergic DNA Binding System Assisted by Orthogonal γPNA Dimerization Domains with Cooperativity and Versatility

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Artificial Assemblies with Cooperative DNA Recognition

Part of the book series: Springer Theses ((Springer Theses))

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Abstract

Synthetic molecules capable of DNA binding and mimicking cooperation of transcription factor (TF) pairs have long been considered as a promising tool for manipulating gene expression. Our previous reported PIP–HoGu system, a programmable DNA binder pyrrole–imidazole polyamides (PIPs) conjugated to host–guest moiety, defined a general framework for mimicking cooperative TF pair–DNA interactions. Here, we supplanted the cooperation modules with left-handed (LH) γPNA modules: i.e., PIPs conjugated with nucleic acid-based cooperation system (PIP–NaCo). LH γPNA was chosen due to its bioorthogonality, sequence specific interaction, and high binding affinity toward the partner strand. The cooperativity is highly comparable with natural TF pair-DNA system, with a minimum energetics of cooperation of −3.27 kcal mol−1. Moreover, through changing the linker conjugation site, binding mode, and the length of γPNAs sequence, the cooperative energetics of PIP–NaCo can be tuned independently and reasonably. Current PIP–NaCo platform might also have the potential for precise manipulation of biological processes through the constitution of triple to multiple hetero binding systems.

This chapter is reprinted and modified with permission from “Z. YU, W.C. Hsieh, S. Asamitsu, K. Hashiya, T. Bando, D.H. Ly, H. Sugiyama, Orthogonal gammaPNA Dimerization Domains Empower DNA Binders with Cooperativity and Versatility Mimicking that of Transcription Factor Pairs, Chem. Eur. J., 24 (2018) 14183–14188”. Copyright 2018 John Wiley and Sons.

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References

  1. Yu Z, Hsieh WC, Asamitsu S et al (2018) Orthogonal gammaPNA dimerization domains empower DNA binders with cooperativity and versatility mimicking that of transcription factor pairs. Chem Eur J 24:14183–14188

    Article  CAS  Google Scholar 

  2. Jolma A, Yan J, Whitington T et al (2013) DNA-binding specificities of human transcription factors. Cell 152:327–339

    Article  CAS  Google Scholar 

  3. Morgunova E, Taipale J (2017) Structural perspective of cooperative transcription factor binding. Curr Opin Struct Biol 47:1–8

    Article  CAS  Google Scholar 

  4. Stampfel G, Kazmar T, Frank O et al (2015) Transcriptional regulators form diverse groups with context-dependent regulatory functions. Nature 528:147–151

    Article  CAS  Google Scholar 

  5. Ng CK, Li NX, Chee S et al (2012) Deciphering the Sox-Oct partner code by quantitative cooperativity measurements. Nucleic Acids Res 40:4933–4941

    Article  CAS  Google Scholar 

  6. Jolma A, Yin Y, Nitta KR et al (2015) DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527:384–388

    CAS  Google Scholar 

  7. Hoverter NP, Zeller MD, McQuade MM et al (2014) The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition. Nucleic Acids Res 42:13615–13632

    Article  CAS  Google Scholar 

  8. Ravindranath AJ, Cadigan KM (2016) The role of the C-clamp in Wnt-related colorectal cancers. Cancers 8:74

    Article  Google Scholar 

  9. Gottesfeld JM, Neely L, Trauger JW et al (1997) Regulation of gene expression by small molecules. Nature 387:202–205

    Article  CAS  Google Scholar 

  10. Dragulescu-Andrasi A, Rapireddy S, He G et al (2006) Cell-permeable peptide nucleic acid designed to bind to the 5-untranslated region of E-cadherin transcript induces potent and sequence-specific antisense effects. J Am Chem Soc 128:16104–16112

    Article  CAS  Google Scholar 

  11. Taniguchi J, Pandian GN, Hidaka T et al (2017) A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm. Nucleic Acids Res 45:9219–9228

    Article  CAS  Google Scholar 

  12. Pazos E, Mosquera J, Vázquez ME et al (2011) DNA recognition by synthetic constructs. ChemBioChem 12:1958–1973

    Article  CAS  Google Scholar 

  13. Wang M, Yu Y, Liang C et al (2016) Recent advances in developing small molecules targeting nucleic acid. Int J Mol Sci 17:779

    Article  Google Scholar 

  14. Olalla V, Eugenio VM, Blanco BJ et al (2007) Specific DNA recognition by a synthetic, monomeric Cys2His2 zinc-finger peptide conjugated to a minor-groove binder. Angew Chem Int Ed Engl 46:6886–6890

    Article  Google Scholar 

  15. Ueno M, Murakami A, Makino K et al (1993) Arranging quaternary structure of peptides by cyclodextrin-guest inclusion complex: sequence-specific DNA binding by a peptide dimer with artificial dimerization module. J Am Chem Soc 115:12575–12576

    Article  CAS  Google Scholar 

  16. Distefano MD, Dervan PB (1993) Energetics of cooperative binding of oligonucleotides with discrete dimerization domains to DNA by triple helix formation. Proc Natl Acad Sci USA 90:1179–1183

    Article  CAS  Google Scholar 

  17. Blanco JB, Dodero VI, Vázquez ME et al (2006) Sequence-specific DNA binding by noncovalent peptide-tripyrrole conjugates. Angew Chem Int Ed Engl 45:8210–8214

    Article  CAS  Google Scholar 

  18. Sánchez MI, Mosquera J, Vázquez ME et al (2014) Reversible supramolecular assembly at specific DNA sites: nickel-promoted bivalent DNA binding with designed peptide and Bipyridyl–Bis(benzamidine) components. Angew Chem Int Ed Engl 53:9917–9921

    Article  Google Scholar 

  19. Chang D, Kim KT, Lindberg E et al (2018) Accelerating turnover frequency in nucleic acid templated reactions. Bioconjugate Chem 29:158–163

    Article  CAS  Google Scholar 

  20. Trauger JW, Baird EE, Dervan PB (1996) Recognition of DNA by designed ligands at subnanomolar concentrations. Nature 382:559–561

    Article  CAS  Google Scholar 

  21. Yu Z, Pandian GN, Hidaka T et al (2019) Therapeutic gene regulation using pyrrole-imidazole polyamides. Adv Drug Deliv Rev 147:66–85

    Article  CAS  Google Scholar 

  22. Yu Z, Guo C, Wei Y et al (2018) Pip-HoGu: an artificial assembly with cooperative DNA recognition capable of mimicking transcription factor pairs. J Am Chem Soc 140:2426–2429

    Article  CAS  Google Scholar 

  23. Singleton SF, Dervan PB (1992) Influence of pH on the equilibrium association constants for oligodeoxyribonucleotide-directed triple helix formation at single DNA sites. Biochemistry 31:10995–11003

    Article  CAS  Google Scholar 

  24. Yu Z, Ai M, Samanta SK et al (2020) A synthetic transcription factor pair mimic for precise recruitment of an epigenetic modifier to the targeted DNA locus. Chem Commun 56:2296–2299

    Google Scholar 

  25. Egholm M, Buchardt O, Christensen L et al (1993) PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 365:566–568

    Article  CAS  Google Scholar 

  26. Berger O, Gazit E (2017) Molecular self-assembly using peptide nucleic acids. Pept Sci 108:e22930

    Article  Google Scholar 

  27. Ellipilli S, Ganesh KN (2015) Fluorous peptide nucleic acids: PNA analogues with fluorine in backbone (γ-CF2-apg-PNA) enhance cellular uptake. J Org Chem 80:9185–9191

    Article  CAS  Google Scholar 

  28. Sahu B, Chenna V, Lathrop KL et al (2009) Synthesis of conformationally preorganized and cell-permeable guanidine-based γ-peptide nucleic acids (γGPNAs). J Org Chem 74:1509–1516

    Article  CAS  Google Scholar 

  29. Dragulescu-Andrasi A, Rapireddy S, Frezza BM et al (2006) A simple gamma-backbone modification preorganizes peptide nucleic acid into a helical structure. J Am Chem Soc 128:10258–10267

    Article  CAS  Google Scholar 

  30. Jain DR, Anandi VL, Lahiri M et al (2014) Influence of pendant chiral Cγ-(alkylideneamino/guanidino) cationic side-chains of PNA backbone on hybridization with complementary DNA/RNA and cell permeability. J Org Chem 79:9567–9577

    Article  CAS  Google Scholar 

  31. Manna A, Rapireddy S, Sureshkumar G et al (2015) Synthesis of optically pure γPNA monomers: a comparative study. Tetrahedron 71:3507–3514

    Article  CAS  Google Scholar 

  32. Sacui I, Hsieh W-C, Manna A et al (2015) Gamma peptide nucleic acids: as orthogonal nucleic acid recognition codes for organizing molecular self-assembly. J Am Chem Soc 137:8603–8610

    Article  CAS  Google Scholar 

  33. Kameshima W, Ishizuka T, Minoshima M et al (2013) Conjugation of peptide nucleic acid with a pyrrole/imidazole polyamide to specifically recognize and cleave DNA. Angew Chem Int Ed Engl 52:13681–13684

    Article  CAS  Google Scholar 

  34. Sahu B, Sacui I, Rapireddy S et al (2011) Synthesis and characterization of conformationally preorganized, (R)-diethylene glycol-containing γ-peptide nucleic acids with superior hybridization properties and water solubility. J Org Chem 76:5614–5627

    Article  CAS  Google Scholar 

  35. Yu Z, Taniguchi J, Wei Y et al (2017) Antiproliferative and apoptotic activities of sequence-specific histone acetyltransferase inhibitors. Eur J Med Chem 138:320–327

    Article  CAS  Google Scholar 

  36. Kadhane U, Holm AIS, Hoffmann SV et al (2008) Strong coupling between adenine nucleobases in DNA single strands revealed by circular dichroism using synchrotron radiation. Phys Rev E 77:021901

    Article  Google Scholar 

  37. Fischer E (1894) Einfluss der Configuration auf die Wirkung der Enzyme. Ber Dtsch Chem Ges 27:2985–2993

    Article  CAS  Google Scholar 

  38. Wittung P, Eriksson M, Lyng R et al (1995) Induced chirality in PNA-PNA duplexes. J Am Chem Soc 117:10167–10173

    Article  CAS  Google Scholar 

  39. Moretti R, Donato LJ, Brezinski ML et al (2008) Targeted chemical wedges reveal the role of allosteric DNA modulation in protein-DNA assembly, ACS. Chem Biol 3:220–229

    CAS  Google Scholar 

  40. Zhang DY, Seelig G (2011) Dynamic DNA nanotechnology using strand-displacement reactions. Nat Chem 3:103–113

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan

    Zutao YU

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  1. Zutao YU
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YU, Z. (2020). PIP–NaCo, a Synergic DNA Binding System Assisted by Orthogonal γPNA Dimerization Domains with Cooperativity and Versatility. In: Artificial Assemblies with Cooperative DNA Recognition. Springer Theses. Springer, Singapore. https://doi.org/10.1007/978-981-15-4423-1_3

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