Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Helical polymers for biological and medical applications

Nature Reviews Chemistry volume 4, pages 291–310 (2020)Cite this article

Subjects

Abstract

Helices are the most prevalent secondary structure in biomolecules and play vital roles in their activity. Chemists have been fascinated with mimicking this molecular conformation with synthetic materials. Research has now been devoted to the synthesis and characterization of helical materials, and to understand the design principles behind this molecular architecture. In parallel, work has been done to develop synthetic polymers for biological and medical applications. We now have access to materials with controlled size, molecular conformation, multivalency or functionality. As a result, synthetic polymers are being investigated in areas such as drug and gene delivery, tissue engineering, imaging and sensing, or as polymer therapeutics. Here, we provide a critical view of where these two fields, helical polymers and polymers for biological and medical applications, overlap. We have selected relevant polymer families and examples to illustrate the range of applications that can be targeted and the impact of the helical conformation on the performance. For each family of polymers, we briefly describe how they can be prepared, what helical conformations are observed and what parameters control helicity. We close this Review with an outlook of the challenges ahead, including the characterization of helicity through the process and the identification of biocompatibility.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Major families of helical polymers discussed in this Review.
Fig. 2: Controlling helical conformation in poly(amino acid)s.
Fig. 3: Antimicrobial and gene-delivery applications of poly(amino acid)s.
Fig. 4: Helical poly(amino acid)s for drug delivery.
Fig. 5: Hydrogels formed from helical polymers.
Fig. 6: Vesicles based on poly(isocyanide)s for nanoreactors and artificial organelles.
Fig. 7: Modulation of helical chirality in poly(acetylene)s through external stimuli.
Fig. 8: The application of helical poly(thiophene)s in biosensing.

Similar content being viewed by others

References

  1. Yalpani, M. in Polysaccharides: Syntheses, Modifications and Structure/Property Relations 8–49 (Elsevier, 1988).

  2. Dumitriu, S. Polysaccharides: Structural Diversity and Functional Versatility (CRC, 2004).

  3. Pauling, L., Corey, R. B. & Branson, H. R. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl Acad. Sci. USA 37, 205–211 (1951).

    Article  CAS  PubMed  Google Scholar 

  4. Young, G. T. & Hardy, P. M. in Amino Acids, Peptides and Proteins Vol. 1 (ed. Young, G. T.) 112–154 (Royal Society of Chemistry, 1969).

  5. Ruso, J. M. & Piñeiro, Á. Proteins in Solution and at Interfaces: Methods and Applications in Biotechnology and Materials Science (Wiley, 2013).

  6. Watson, J. D. & Crick, F. H. C. Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  PubMed  Google Scholar 

  7. Franklin, R. E. & Gosling, R. G. Molecular configuration in sodium thymonucleate. Nature 171, 740–741 (1953).

    Article  CAS  PubMed  Google Scholar 

  8. Ghosh, A. & Bansal, M. A glossary of DNA structures from A to Z. Acta Crystallogr. D Biol. Crystallogr. 59, 620–626 (2003).

    Article  PubMed  CAS  Google Scholar 

  9. Nakamura, Y. in Starch: Metabolism and Structure 1–90 (Springer, 2015).

  10. Walters, R. F. S. & DeGrado, W. F. Helix-packing motifs in membrane proteins. Proc. Natl Acad. Sci. USA 103, 13658–13663 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Barth, P. & Senes, A. Toward high-resolution computational design of the structure and function of helical membrane proteins. Nat. Struct. Mol. Biol. 23, 475–480 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prockop, D. J. & Kivirikko, K. I. Collagens: molecular biology, diseases, and potentials for therapy. Annu. Rev. Biochem. 64, 403–434 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. Karsdal, M. Biochemistry of Collagens, Laminins and Elastin: Structure, Function and Biomarkers (Elsevier Science, 2016).

  14. Travers, A. & Muskhelishvili, G. DNA structure and function. FEBS J. 282, 2279–2295 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Nelson, D. L., Lehninger, A. L. & Cox, M. M. Lehninger Principles of Biochemistry (Rediff Books, 2017).

  16. Hecht, S. & Huc, I. Foldamers (Wiley, 2007).

  17. Yashima, E., Maeda, K., Iida, H., Furusho, Y. & Nagai, K. Helical polymers: synthesis, structures, and functions. Chem. Rev. 109, 6102–6211 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Nakano, T. & Okamoto, Y. in Polymer Science: A Comprehensive Reference (eds Matyjaszewski, K. & Möller, M.) 629–687 (Elsevier, 2012).

  19. Ren, Z. & Gao, P.-X. A review of helical nanostructures: growth theories, synthesis strategies and properties. Nanoscale 6, 9366–9400 (2014).

    Article  CAS  PubMed  Google Scholar 

  20. Yashima, E. et al. Supramolecular helical systems: helical assemblies of small molecules, foldamers, and polymers with chiral amplification and their functions. Chem. Rev. 116, 13752–13990 (2016).

    Article  CAS  PubMed  Google Scholar 

  21. Green, J. J. & Elisseeff, J. H. Mimicking biological functionality with polymers for biomedical applications. Nature 540, 386–394 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. Scholz, C. Polymers for Biomedicine: Synthesis, Characterization, and Applications (Wiley, 2017).

  23. Deming, T. J. et al. Polymers at the interface with biology. Biomacromolecules 19, 3151–3162 (2018).

    Article  PubMed  Google Scholar 

  24. Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15, 541–555 (2014).

    Article  CAS  PubMed  Google Scholar 

  25. Mitragotri, S., Burke, P. A. & Langer, R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat. Rev. Drug Discov. 13, 655–672 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stewart, M. P. et al. In vitro and ex vivo strategies for intracellular delivery. Nature 538, 183–192 (2016).

    Article  CAS  PubMed  Google Scholar 

  27. Kakkar, A., Traverso, G., Farokhzad, O. C., Weissleder, R. & Langer, R. Evolution of macromolecular complexity in drug delivery systems. Nat. Rev. Chem. 1, 0063 (2017).

    Article  CAS  Google Scholar 

  28. Ekladious, I., Colson, Y. L. & Grinstaff, M. W. Polymer–drug conjugate therapeutics: advances, insights and prospects. Nat. Rev. Drug Discov. 18, 273–294 (2019).

    Article  CAS  PubMed  Google Scholar 

  29. Lostalé-Seijo, I. & Montenegro, J. Synthetic materials at the forefront of gene delivery. Nat. Rev. Chem. 2, 258–277 (2018).

    Article  Google Scholar 

  30. Celiz, A. D. et al. Materials for stem cell factories of the future. Nat. Mater. 13, 570–579 (2014).

    Article  CAS  PubMed  Google Scholar 

  31. Khademhosseini, A. & Langer, R. A decade of progress in tissue engineering. Nat. Protoc. 11, 1775–1781 (2016).

    Article  CAS  PubMed  Google Scholar 

  32. Laurent, J. et al. Convergence of microengineering and cellular self-organization towards functional tissue manufacturing. Nat. Biomed. Eng. 1, 939–956 (2017).

    Article  CAS  PubMed  Google Scholar 

  33. Xia, H. et al. Tissue repair and regeneration with endogenous stem cells. Nat. Rev. Mater. 3, 174–193 (2018).

    Article  CAS  Google Scholar 

  34. Elsabahy, M., Heo, G. S., Lim, S.-M., Sun, G. & Wooley, K. L. Polymeric nanostructures for imaging and therapy. Chem. Rev. 115, 10967–11011 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fuchs, A. V., Gemmell, A. C. & Thurecht, K. J. Utilising polymers to understand diseases: advanced molecular imaging agents. Polym. Chem. 6, 868–880 (2015).

    Article  CAS  Google Scholar 

  36. Yu, J., Rong, Y., Kuo, C.-T., Zhou, X.-H. & Chiu, D. T. Recent advances in the development of highly luminescent semiconducting polymer dots and nanoparticles for biological imaging and medicine. Anal. Chem. 89, 42–56 (2017).

    Article  CAS  PubMed  Google Scholar 

  37. Hu, L., Zhang, Q., Li, X. & Serpe, M. J. Stimuli-responsive polymers for sensing and actuation. Mater. Horiz. 6, 1774–1793 (2019).

    Article  CAS  Google Scholar 

  38. Rodríguez-Hernández, J. Polymers Against Microorganisms: On the Race to Efficient Antimicrobial Materials (Springer, 2017).

  39. Hartlieb, M., Williams, E. G. L., Kuroki, A., Perrier, S. & Locock, K. E. S. Antimicrobial polymers: mimicking amino acid functionality, sequence control and three-dimensional structure of host-defense peptides. Curr. Med. Chem. 24, 2115–2140 (2017).

    Article  CAS  PubMed  Google Scholar 

  40. Ergene, C., Yasuhara, K. & Palermo, E. F. Biomimetic antimicrobial polymers: recent advances in molecular design. Polym. Chem. 9, 2407–2427 (2018).

    Article  CAS  Google Scholar 

  41. Deming, T. J. Synthetic polypeptides for biomedical applications. Prog. Polym. Sci. 32, 858–875 (2007).

    Article  CAS  Google Scholar 

  42. Deng, C. et al. Functional polypeptide and hybrid materials: precision synthesis via α-amino acid N-carboxyanhydride polymerization and emerging biomedical applications. Prog. Polym. Sci. 39, 330–364 (2014).

    Article  CAS  Google Scholar 

  43. Zagorodko, O., Arroyo-Crespo, J. J., Nebot, V. J. & Vicent, M. J. Polypeptide-based conjugates as therapeutics: opportunities and challenges. Macromol. Biosci. 17, 1600316 (2017).

    Article  CAS  Google Scholar 

  44. Song, Z. et al. Synthetic polypeptides: from polymer design to supramolecular assembly and biomedical application. Chem. Soc. Rev. 46, 6570–6599 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Deming, T. J. in Polymer Science: A Comprehensive Reference (eds Matyjaszewski, K. & Möller, M.) 427–449 (Elsevier, 2012).

  46. Cheng, J. & Deming, T. J. in Peptide-Based Materials (ed. Deming, T.) 1–26 (Springer, 2012).

  47. Jiang, Z., Chen, J., Ding, J., Zhuang, X. & Chen, X. in Advances in Bioinspired and Biomedical Materials Vol. 1 (eds Ito, Y., Chen, X. & Kang, I.-K.) 149–170 (American Chemical Society, 2017).

  48. Urnes, P. & Doty, P. in Advances in Protein Chemistry Vol. 16 (eds Anfinsen, C. B. Jr, Anson, M. L., Bailey, K. & Edsall, J. T.) 401–544 (Academic, 1962).

  49. Katchalski, E., Sela, M., Silman, H. I. & Berger, A. in The Proteins: Composition, Structure and Function (ed. Neurath, H.) 405–602 (Academic, 1964).

  50. Ramachandran, G. N. & Sasisekharan, V. in Advances in Protein Chemistry Vol. 23 (eds Anfinsen, C. B. Jr, Anson, M. L., Edsall, J. T. & Richards, F. M.) 283–437 (Academic, 1968).

  51. Dill, K. A. Dominant forces in protein folding. Biochemistry 29, 7133–7155 (1990).

    Article  CAS  PubMed  Google Scholar 

  52. Chou, P. Y. & Fasman, G. D. in Advances in Enzymology and Related Areas of Molecular Biology (ed. Purich, D.) 45–148 (Wiley, 1979).

  53. Bonduelle, C. Secondary structures of synthetic polypeptide polymers. Polym. Chem. 9, 1517–1529 (2018).

    Article  CAS  Google Scholar 

  54. Song, Z. et al. Secondary structures in synthetic polypeptides from N-carboxyanhydrides: design, modulation, association, and material applications. Chem. Soc. Rev. 47, 7401–7425 (2018).

    Article  CAS  PubMed  Google Scholar 

  55. Chou, P. Y. & Fasman, G. D. Conformational parameters for amino acids in helical, β-sheet, and random coil regions calculated from proteins. Biochemistry 13, 211–222 (1974).

    Article  CAS  PubMed  Google Scholar 

  56. Chou, P. Y. & Fasman, G. D. Prediction of protein conformation. Biochemistry 13, 222–245 (1974).

    Article  CAS  PubMed  Google Scholar 

  57. Sasisekharan, V. Structure of poly-l-proline. II. Acta Crystallogr. 12, 897–903 (1959).

    Article  CAS  Google Scholar 

  58. MacArthur, M. W. & Thornton, J. M. Influence of proline residues on protein conformation. J. Mol. Biol. 218, 397–412 (1991).

    Article  CAS  PubMed  Google Scholar 

  59. Adzhubei, A. A., Sternberg, M. J. E. & Makarov, A. A. Polyproline-II helix in proteins: structure and function. J. Mol. Biol. 425, 2100–2132 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Creamer, T. P. & Campbell, M. N. in Advances in Protein Chemistry Vol. 62 (ed. Rose, G. D.) 263–282 (Academic, 2002).

  61. Shi, Z., Chen, K., Liu, Z. & Kallenbach, N. R. Conformation of the backbone in unfolded proteins. Chem. Rev. 106, 1877–1897 (2006).

    Article  CAS  PubMed  Google Scholar 

  62. Rath, A., Davidson, A. R. & Deber, C. M. The structure of “unstructured” regions in peptides and proteins: role of the polyproline II helix in protein folding and recognition. Pept. Sci. 80, 179–185 (2005).

    Article  CAS  Google Scholar 

  63. Song, Z. et al. Enzyme-mimetic self-catalyzed polymerization of polypeptide helices. Nat. Commun. 10, 5470 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. De Greef, T. F. A. et al. Supramolecular polymerization. Chem. Rev. 109, 5687–5754 (2009).

    Article  PubMed  CAS  Google Scholar 

  65. Aragonès, A. C. et al. Electrostatic catalysis of a Diels–Alder reaction. Nature 531, 88–91 (2016).

    Article  PubMed  CAS  Google Scholar 

  66. Baumgartner, R., Fu, H., Song, Z., Lin, Y. & Cheng, J. Cooperative polymerization of α-helices induced by macromolecular architecture. Nat. Chem. 9, 614–622 (2017).

    Article  CAS  PubMed  Google Scholar 

  67. Chen, C. et al. Proximity-induced cooperative polymerization in “hinged” helical polypeptides. J. Am. Chem. Soc. 141, 8680–8683 (2019).

    Article  CAS  PubMed  Google Scholar 

  68. Song, Z. et al. Synthesis of polypeptides via bioinspired polymerization of in situ purified N-carboxyanhydrides. Proc. Natl Acad. Sci. USA 116, 10658–10663 (2019).

    Article  CAS  PubMed  Google Scholar 

  69. Olander, D. S. & Holtzer, A. The stability of the polyglutamic acid alpha helix. J. Am. Chem. Soc. 90, 4549–4560 (1968).

    Article  CAS  PubMed  Google Scholar 

  70. Tomimatsu, Y., Vitello, L. & Gaffield, W. Effect of aggregation on the optical rotatory dispersion of poly(α,l-glutamic acid). Biopolymers 4, 653–662 (1966).

    Article  CAS  Google Scholar 

  71. Saudek, V., Štokrová, Š. & Schmidt, P. Conformational study of poly(α-l-aspartic acid). Biopolymers 21, 1011–1020 (1982).

    Article  CAS  Google Scholar 

  72. Lu, H. et al. Ionic polypeptides with unusual helical stability. Nat. Commun. 2, 206 (2011). Demonstrates that stable, water-soluble, ionic, helical poly(amino acid)s can be prepared if the helical conformation is stabilized by additional secondary interactions between the side chains, in this case, van der Waals forces.

    Article  PubMed  CAS  Google Scholar 

  73. Zhang, Y., Lu, H., Lin, Y. & Cheng, J. Water-soluble polypeptides with elongated, charged side chains adopt ultrastable helical conformations. Macromolecules 44, 6641–6644 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Engler, A. C., Lee, H. & Hammond, P. T. Highly efficient “grafting onto” a polypeptide backbone using click chemistry. Angew. Chem. Int. Ed. 48, 9334–9338 (2009).

    Article  CAS  Google Scholar 

  75. Engler, A. C., Bonner, D. K., Buss, H. G., Cheung, E. Y. & Hammond, P. T. The synthetic tuning of clickable pH responsive cationic polypeptides and block copolypeptides. Soft Matter 7, 5627–5637 (2011).

    Article  CAS  Google Scholar 

  76. Xiao, C. et al. Facile synthesis of glycopolypeptides by combination of ring-opening polymerization of an alkyne-substituted N-carboxyanhydride and click “glycosylation”. Macromol. Rapid Commun. 31, 991–997 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Kramer, J. R. & Deming, T. J. Preparation of multifunctional and multireactive polypeptides via methionine alkylation. Biomacromolecules 13, 1719–1723 (2012).

    Article  CAS  PubMed  Google Scholar 

  78. Kramer, J. R. & Deming, T. J. Reversible chemoselective tagging and functionalization of methionine containing peptides. Chem. Commun. 49, 5144–5146 (2013).

    Article  CAS  Google Scholar 

  79. Kramer, J. R. et al. Reinventing cell penetrating peptides using glycosylated methionine sulfonium ion sequences. ACS Cent. Sci. 1, 83–88 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Deming, T. J. Functional modification of thioether groups in peptides, polypeptides, and proteins. Bioconjug. Chem. 28, 691–700 (2017).

    Article  CAS  PubMed  Google Scholar 

  81. Kramer, J. R. & Deming, T. J. Glycopolypeptides with a redox-triggered helix-to-coil transition. J. Am. Chem. Soc. 134, 4112–4115 (2012).

    Article  CAS  PubMed  Google Scholar 

  82. Kramer, J. R. & Deming, T. J. Multimodal switching of conformation and solubility in homocysteine derived polypeptides. J. Am. Chem. Soc. 136, 5547–5550 (2014).

    Article  CAS  PubMed  Google Scholar 

  83. Zhou, M. N. et al. N-carboxyanhydride polymerization of glycopolypeptides that activate antigen-presenting cells through dectin-1 and dectin-2. Angew. Chem. Int. Ed. 57, 3137–3142 (2018).

    Article  CAS  Google Scholar 

  84. Kramer, J. R. & Deming, T. J. Glycopolypeptides via living polymerization of glycosylated-l-lysine N-carboxyanhydrides. J. Am. Chem. Soc. 132, 15068–15071 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Kramer, J. R., Onoa, B., Bustamante, C. & Bertozzi, C. R. Chemically tunable mucin chimeras assembled on living cells. Proc. Natl Acad. Sci. USA 112, 12574–12579 (2015). Demonstrates that helical conformations other than the α-helix can be obtained for glycosylated poly(amino acid)s, depending on the sugar conjugated and the nature of the linkage.

    Article  CAS  PubMed  Google Scholar 

  86. Brogden, K. A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238–250 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. Fjell, C. D., Hiss, J. A., Hancock, R. E. W. & Schneider, G. Designing antimicrobial peptides: form follows function. Nat. Rev. Drug Discov. 11, 37–51 (2012).

    Article  CAS  Google Scholar 

  88. Stanzl, E. G., Trantow, B. M., Vargas, J. R. & Wender, P. A. Fifteen years of cell-penetrating, guanidinium-rich molecular transporters: basic science, research tools, and clinical applications. Acc. Chem. Res. 46, 2944–2954 (2013).

    Article  CAS  PubMed  Google Scholar 

  89. Copolovici, D. M., Langel, K., Eriste, E. & Langel, Ü. Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8, 1972–1994 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Wyrsta, M. D., Cogen, A. L. & Deming, T. J. A parallel synthetic approach for the analysis of membrane interactive copolypeptides. J. Am. Chem. Soc. 123, 12919–12920 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Koller, D. & Lohner, K. The role of spontaneous lipid curvature in the interaction of interfacially active peptides with membranes. Biochim. Biophys. Acta 1838, 2250–2259 (2014).

    Article  CAS  PubMed  Google Scholar 

  92. Xiong, M. et al. Helical antimicrobial polypeptides with radial amphiphilicity. Proc. Natl Acad. Sci. USA 112, 13155–13160 (2015).

    Article  CAS  PubMed  Google Scholar 

  93. Xiong, M. et al. Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides. Proc. Natl Acad. Sci. USA 114, 12675–12680 (2017).

    Article  CAS  PubMed  Google Scholar 

  94. Xiong, M. et al. Bacteria-assisted activation of antimicrobial polypeptides by a random-coil to helix transition. Angew. Chem. Int. Ed. 56, 10826–10829 (2017).

    Article  CAS  Google Scholar 

  95. Lam, S. J. et al. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat. Microbiol. 1, 16162 (2016).

    Article  CAS  PubMed  Google Scholar 

  96. Shirbin, S. J. et al. Architectural effects of star-shaped “structurally nanoengineered antimicrobial peptide polymers” (SNAPPs) on their biological activity. Adv. Healthc. Mater. 7, 1800627 (2018).

    Article  CAS  Google Scholar 

  97. Engler, A. C. et al. Effects of side group functionality and molecular weight on the activity of synthetic antimicrobial polypeptides. Biomacromolecules 12, 1666–1674 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. Ahmed, M. Peptides, polypeptides and peptide–polymer hybrids as nucleic acid carriers. Biomater. Sci. 5, 2188–2211 (2017).

    Article  CAS  PubMed  Google Scholar 

  99. Chen, J., Guan, X., Hu, Y., Tian, H. & Chen, X. in Polymeric Gene Delivery Systems (ed. Cheng, Y.) 85–112 (Springer, (2017).

  100. Miyata, K., Nishiyama, N. & Kataoka, K. Rational design of smart supramolecular assemblies for gene delivery: chemical challenges in the creation of artificial viruses. Chem. Soc. Rev. 41, 2562–2574 (2012).

    Article  CAS  PubMed  Google Scholar 

  101. Mutaf, O. F., Kishimura, A., Mochida, Y., Kim, A. & Kataoka, K. Induction of secondary structure through micellization of an oppositely charged pair of homochiral block- and homopolypeptides in an aqueous medium. Macromol. Rapid Commun. 36, 1958–1964 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Perry, S. L. et al. Chirality-selected phase behaviour in ionic polypeptide complexes. Nat. Commun. 6, 6052 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gabrielson, N. P. et al. Reactive and bioactive cationic α-helical polypeptide template for nonviral gene delivery. Angew. Chem. Int. Ed. 51, 1143–1147 (2012).

    Article  CAS  Google Scholar 

  104. Gabrielson, N. P., Lu, H., Yin, L., Kim, K. H. & Cheng, J. A cell-penetrating helical polymer for siRNA delivery to mammalian cells. Mol. Ther. 20, 1599–1609 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wang, H.-X. et al. Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide. Proc. Natl Acad. Sci. USA 115, 4903–4908 (2018).

    Article  CAS  PubMed  Google Scholar 

  106. Yin, L. et al. Non-viral gene delivery via membrane-penetrating, mannose-targeting supramolecular self-assembled nanocomplexes. Adv. Mater. 25, 3063–3070 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. He, H. et al. Suppression of hepatic inflammation via systemic siRNA delivery by membrane-disruptive and endosomolytic helical polypeptide hybrid nanoparticles. ACS Nano 10, 1859–1870 (2016).

    Article  CAS  PubMed  Google Scholar 

  108. Liu, Y. et al. Systemic siRNA delivery to tumors by cell-penetrating α-helical polypeptide-based metastable nanoparticles. Nanoscale 10, 15339–15349 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Yin, L. et al. Light-responsive helical polypeptides capable of reducing toxicity and unpacking DNA: toward nonviral gene delivery. Angew. Chem. Int. Ed. 52, 9182–9186 (2013).

    Article  CAS  Google Scholar 

  110. Zheng, N. et al. Manipulating the membrane penetration mechanism of helical polypeptides via aromatic modification for efficient gene delivery. Acta Biomater. 58, 146–157 (2017).

    Article  CAS  PubMed  Google Scholar 

  111. Li, F. et al. Engineering the aromaticity of cationic helical polypeptides toward “self-activated” DNA/siRNA delivery. ACS Appl. Mater. Interfaces 9, 23586–23601 (2017).

    Article  CAS  PubMed  Google Scholar 

  112. Dang, J. et al. Multivalency-assisted membrane-penetrating siRNA delivery sensitizes photothermal ablation via inhibition of tumor glycolysis metabolism. Biomaterials 223, 119463 (2019).

    Article  CAS  PubMed  Google Scholar 

  113. Pelegri-O’Day, E. M., Lin, E.-W. & Maynard, H. D. Therapeutic protein–polymer conjugates: advancing beyond PEGylation. J. Am. Chem. Soc. 136, 14323–14332 (2014).

    Article  PubMed  CAS  Google Scholar 

  114. Hou, Y. et al. Therapeutic protein PEPylation: the helix of nonfouling synthetic polypeptides minimizes antidrug antibody generation. ACS Cent. Sci. 5, 229–236 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Zhang, C. et al. From neutral to zwitterionic poly(α-amino acid) nonfouling surfaces: effects of helical conformation and anchoring orientation. Biomaterials 178, 728–737 (2018).

    Article  CAS  PubMed  Google Scholar 

  116. Cabral, H. & Kataoka, K. Progress of drug-loaded polymeric micelles into clinical studies. J. Control. Release 190, 465–476 (2014).

    Article  CAS  PubMed  Google Scholar 

  117. Cabral, H., Miyata, K., Osada, K. & Kataoka, K. Block copolymer micelles in nanomedicine applications. Chem. Rev. 118, 6844–6892 (2018).

    Article  CAS  PubMed  Google Scholar 

  118. Olsen, B. D. & Segalman, R. A. Self-assembly of rod–coil block copolymers. Mater. Sci. Eng. R. Rep. 62, 37–66 (2008).

    Article  CAS  Google Scholar 

  119. Holowka, E. P., Pochan, D. J. & Deming, T. J. Charged polypeptide vesicles with controllable diameter. J. Am. Chem. Soc. 127, 12423–12428 (2005).

    Article  CAS  PubMed  Google Scholar 

  120. Holowka, E. P., Sun, V. Z., Kamei, D. T. & Deming, T. J. Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat. Mater. 6, 52–57 (2007).

    Article  CAS  PubMed  Google Scholar 

  121. Choe, U.-J. et al. Endocytosis and intracellular trafficking properties of transferrin-conjugated block copolypeptide vesicles. Biomacromolecules 14, 1458–1464 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Schatz, C., Louguet, S., Le Meins, J. & Lecommandoux, S. Polysaccharide-block-polypeptide copolymer vesicles: towards synthetic viral capsids. Angew. Chem. Int. Ed. 48, 2572–2575 (2009).

    Article  CAS  Google Scholar 

  123. Upadhyay, K. K. et al. The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(γ-benzyl l-glutamate)-b-hyaluronan polymersomes. Biomaterials 31, 2882–2892 (2010).

    Article  CAS  PubMed  Google Scholar 

  124. Quadir, M. A., Martin, M. & Hammond, P. T. Clickable synthetic polypeptides–routes to new highly adaptive biomaterials. Chem. Mater. 26, 461–476 (2014).

    Article  CAS  Google Scholar 

  125. Quadir, M. A. et al. Ligand-decorated click polypeptide derived nanoparticles for targeted drug delivery applications. Nanomedicine 13, 1797–1808 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Mochida, Y. et al. Bundled assembly of helical nanostructures in polymeric micelles loaded with platinum drugs enhancing therapeutic efficiency against pancreatic tumor. ACS Nano 8, 6724–6738 (2014). Demonstrates that the helical conformation can be induced upon loading of a drug, improving not only the mechanical properties of the formed micelles but also their pharmaceutical properties.

    Article  CAS  PubMed  Google Scholar 

  127. Cabral, H. et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotechnol. 6, 815–823 (2011).

    Article  CAS  PubMed  Google Scholar 

  128. Peppas, N. A. Hydrogels in Medicine and Pharmacy: Properties and Applications Vol. 3 (CRC, 2019).

  129. Nowak, A. P. et al. Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles. Nature 417, 424–428 (2002). Demonstrates that the helical conformation has a significant impact on the mechanical properties of synthetic hydrogels, paving the way to the application of these materials for tissue engineering and drug delivery.

    Article  CAS  PubMed  Google Scholar 

  130. Breedveld, V., Nowak, A. P., Sato, J., Deming, T. J. & Pine, D. J. Rheology of block copolypeptide solutions: hydrogels with tunable properties. Macromolecules 37, 3943–3953 (2004).

    Article  CAS  Google Scholar 

  131. Deming, T. J. Polypeptide hydrogels via a unique assembly mechanism. Soft Matter 1, 28–35 (2005).

    Article  CAS  PubMed  Google Scholar 

  132. Zhang, S., Alvarez, D. J., Sofroniew, M. V. & Deming, T. J. Design and synthesis of nonionic copolypeptide hydrogels with reversible thermoresponsive and tunable physical properties. Biomacromolecules 16, 1331–1340 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Wollenberg, A. L. et al. Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery. Biomaterials 178, 527–545 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Anderson, M. A. et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 532, 195–200 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Anderson, M. A. et al. Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature 561, 396–400 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Schwartz, E., Koepf, M., Kitto, H. J., Nolte, R. J. M. & Rowan, A. E. Helical poly(isocyanides): past, present and future. Polym. Chem. 2, 33–47 (2011).

    Article  CAS  Google Scholar 

  137. Akeroyd, N., Nolte, R. J. M. & Rowan, A. E. in Isocyanide Chemistry: Applications in Synthesis and Material Science (Wiley, 2012).

  138. Kollmar, C. & Hoffmann, R. Polyisocyanides: electronic or steric reasons for their presumed helical structure? J. Am. Chem. Soc. 112, 8230–8238 (1990).

    Article  CAS  Google Scholar 

  139. Clericuzio, M., Alagona, G., Ghio, C. & Salvadori, P. Theoretical investigations on the structure of poly(iminomethylenes) with aliphatic side chains. Conformational studies and comparison with experimental spectroscopic data. J. Am. Chem. Soc. 119, 1059–1071 (1997).

    Article  CAS  Google Scholar 

  140. Hase, Y. et al. Mechanism of helix induction in poly(4-carboxyphenyl isocyanide) with chiral amines and memory of the macromolecular helicity and its helical structures. J. Am. Chem. Soc. 131, 10719–10732 (2009).

    Article  CAS  PubMed  Google Scholar 

  141. Cornelissen, J. J. L. M. et al. β-Helical polymers from isocyanopeptides. Science 293, 676–680 (2001). Describes the preparation of poly(isocyanide)s with stable helicity in aqueous conditions as a result of the H-bond network formed between the peptide side chains.

    Article  CAS  PubMed  Google Scholar 

  142. Kouwer, P. H. J. et al. Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 493, 651–655 (2013).

    Article  CAS  PubMed  Google Scholar 

  143. Das, R. K., Gocheva, V., Hammink, R., Zouani, O. F. & Rowan, A. E. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat. Mater. 15, 318–325 (2016).

    Article  CAS  PubMed  Google Scholar 

  144. de Almeida, P. et al. Cytoskeletal stiffening in synthetic hydrogels. Nat. Commun. 10, 609 (2019). Reports the use of β-helical poly(isocyanide)s to form strain-stiffening gels that mimic the mechanical properties of the extracellular matrix.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. op ‘t Veld, R. C. et al. Thermosensitive biomimetic polyisocyanopeptide hydrogels may facilitate wound repair. Biomaterials 181, 392–401 (2018).

    Article  PubMed  CAS  Google Scholar 

  146. Cornelissen, J. J. L. M., Fischer, M., Sommerdijk, N. A. J. M. & Nolte, R. J. M. Helical superstructures from charged poly(styrene)-poly(isocyanodipeptide) block copolymers. Science 280, 1427–1430 (1998).

    Article  CAS  PubMed  Google Scholar 

  147. Vriezema, D. M. et al. Vesicles and polymerized vesicles from thiophene-containing rod–coil block copolymers. Angew. Chem. Int. Ed. 42, 772–776 (2003). Reports the use of poly(isocyanide)s to prepare block copolymers that can afford vesicles in both organic and aqueous conditions, as a result of the unique solubility of the poly(isocyanide) block and its helical conformation.

    Article  CAS  Google Scholar 

  148. van Oers, M. C. M., Rutjes, F. P. J. T. & van Hest, J. C. M. Cascade reactions in nanoreactors. Curr. Opin. Biotechnol. 28, 10–16 (2014).

    Article  PubMed  CAS  Google Scholar 

  149. Che, H. & van Hest, J. C. M. Adaptive polymersome nanoreactors. ChemNanoMat 5, 1092–1109 (2019).

    Article  CAS  Google Scholar 

  150. Vriezema, D. M. et al. Positional assembly of enzymes in polymersome nanoreactors for cascade reactions. Angew. Chem. Int. Ed. 46, 7378–7382 (2007).

    Article  CAS  Google Scholar 

  151. van Dongen, S. F. M., Nallani, M., Cornelissen, J. J. L. M., Nolte, R. J. M. & van Hest, J. C. M. A three-enzyme cascade reaction through positional assembly of enzymes in a polymersome nanoreactor. Chem. Eur. J. 15, 1107–1114 (2009).

    Article  PubMed  CAS  Google Scholar 

  152. Peters, R. J. R. W. et al. Cascade reactions in multicompartmentalized polymersomes. Angew. Chem. Int. Ed. 53, 146–150 (2014).

    Article  CAS  Google Scholar 

  153. Peters, R. J. R. W., Louzao, I. & van Hest, J. C. M. From polymeric nanoreactors to artificial organelles. Chem. Sci. 3, 335–342 (2012).

    Article  CAS  Google Scholar 

  154. Godoy-Gallardo, M., York-Duran, M. J. & Hosta-Rigau, L. Recent progress in micro/nanoreactors toward the creation of artificial organelles. Adv. Healthc. Mater. 7, 1700917 (2018).

    Article  CAS  Google Scholar 

  155. van Dongen, S. F. M. et al. Cellular integration of an enzyme-loaded polymersome nanoreactor. Angew. Chem. Int. Ed. 49, 7213–7216 (2010).

    Article  Google Scholar 

  156. Liu, J., Lam, J. W. Y. & Tang, B. Z. Acetylenic polymers: syntheses, structures, and functions. Chem. Rev. 109, 5799–5867 (2009).

    Article  CAS  PubMed  Google Scholar 

  157. Masuda, T. & Zhang, A. in Handbook of Metathesis (eds Grubbs, R. H., Wenzel, A. G., O’Leary, D. J. & Khosravi, E.) 375–390 (Wiley, 2015).

  158. Simionescu, C. I. & Percec, V. Thermal cis–trans isomerization of cis–transoidal polyphenylacetylene. J. Polym. Sci. Polym. Chem. Ed. 18, 147–155 (1980).

    Article  CAS  Google Scholar 

  159. Percec, V. & Rudick, J. G. Independent electrocyclization and oxidative chain cleavage along the backbone of cis-poly(phenylacetylene). Macromolecules 38, 7241–7250 (2005).

    Article  CAS  Google Scholar 

  160. Masuda, T., Izumikawa, H., Misumi, Y. & Higashimura, T. Stereospecific polymerization of tert-butylacetylene by molybdenum catalysts. Effect of acid-catalyzed geometric isomerization. Macromolecules 29, 1167–1171 (1996).

    Article  CAS  Google Scholar 

  161. Maeda, K. & Yashima, E. Helical polyacetylenes induced via noncovalent chiral interactions and their applications as chiral materials. Top. Curr. Chem. 375, 72 (2017).

    Article  CAS  Google Scholar 

  162. Freire, F., Seco, J. M., Quiñoá, E. & Riguera, R. Chiral amplification and helical-sense tuning by mono- and divalent metals on dynamic helical polymers. Angew. Chem. Int. Ed. 50, 11692–11696 (2011).

    Article  CAS  Google Scholar 

  163. Rodríguez, R., Quiñoá, E., Riguera, R. & Freire, F. Architecture of chiral poly(phenylacetylene)s: from compressed/highly dynamic to stretched/quasi-static helices. J. Am. Chem. Soc. 138, 9620–9628 (2016). A complete description of the dynamic nature of poly(acetylene)s, explored through theoretical, experimental and computational methods.

    Article  PubMed  CAS  Google Scholar 

  164. Cobos, K., Quiñoá, E., Riguera, R. & Freire, F. Chiral-to-chiral communication in polymers: a unique approach to control both helical sense and chirality at the periphery. J. Am. Chem. Soc. 140, 12239–12246 (2018).

    Article  CAS  PubMed  Google Scholar 

  165. Arias, S., Freire, F., Quiñoá, E. & Riguera, R. Nanospheres, nanotubes, toroids, and gels with controlled macroscopic chirality. Angew. Chem. Int. Ed. 53, 13720–13724 (2014).

    Article  CAS  Google Scholar 

  166. Arias, S., Núñez-Martínez, M., Quiñoá, E., Riguera, R. & Freire, F. Simultaneous adjustment of size and helical sense of chiral nanospheres and nanotubes derived from an axially racemic poly(phenylacetylene). Small 13, 1602398 (2017).

    Article  CAS  Google Scholar 

  167. Xu, A., Masuda, T. & Zhang, A. Stimuli-responsive polyacetylenes and dendronized poly(phenylacetylene)s. Polym. Rev. 57, 138–158 (2017).

    Article  CAS  Google Scholar 

  168. Lv, Z., Chen, Z., Shao, K., Qing, G. & Sun, T. Stimuli-directed helical chirality inversion and bio-applications. Polymers 8, 310 (2016).

    Article  PubMed Central  CAS  Google Scholar 

  169. Yashima, E., Nimura, T., Matsushima, T. & Okamoto, Y. Poly((4-dihydroxyborophenyl)acetylene) as a novel probe for chirality and structural assignments of various kinds of molecules including carbohydrates and steroids by circular dichroism. J. Am. Chem. Soc. 118, 9800–9801 (1996). The demonstration that functional poly(acetylene)s can adapt their helical sense and pitch to biologically relevant metabolites, such as a glucose or steroids.

    Article  CAS  Google Scholar 

  170. Hall, D. G. in Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine 1–99 (Wiley, 2005).

  171. Nonokawa, R. & Yashima, E. Detection and amplification of a small enantiomeric imbalance in α-amino acids by a helical poly(phenylacetylene) with crown ether pendants. J. Am. Chem. Soc. 125, 1278–1283 (2003).

    Article  CAS  PubMed  Google Scholar 

  172. Li, B. S. et al. Tuning the chain helicity and organizational morphology of an l-valine-containing polyacetylene by pH change. Nano Lett. 1, 323–328 (2001).

    Article  CAS  Google Scholar 

  173. Arias, S., Freire, F., Calderón, M. & Bergueiro, J. Unexpected chiro-thermoresponsive behavior of helical poly(phenylacetylene)s bearing elastin-based side chains. Angew. Chem. Int. Ed. 56, 11420–11425 (2017). The demonstration that not only can thermoresponsive poly(acetylene)s be prepared but that the arrangement of the thermoresponsive moieties around a helical axis can impact the conformational changes upon heating, resulting in an unexpected increase in solubility.

    Article  CAS  Google Scholar 

  174. Roberts, S., Dzuricky, M. & Chilkoti, A. Elastin-like polypeptides as models of intrinsically disordered proteins. FEBS Lett. 589, 2477–2486 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Bhattacharyya, J., Bellucci, J. J. & Chilkoti, A. in Biomaterials from Nature for Advanced Devices and Therapies (eds Neves, N. M. & Reis, R. L.) 106–126 (Wiley, 2016).

  176. Freire, F., Quiñoá, E. & Riguera, R. Supramolecular assemblies from poly(phenylacetylene)s. Chem. Rev. 116, 1242–1271 (2016).

    Article  CAS  PubMed  Google Scholar 

  177. Zhao, B. & Deng, J. Emulsion polymerization of acetylenics for constructing optically active helical polymer nanoparticles. Polym. Rev. 57, 119–137 (2017).

    Article  CAS  Google Scholar 

  178. Liang, J. & Deng, J. Chiral particles consisting of helical polylactide and helical substituted polyacetylene: preparation and synergistic effects in enantio-differentiating release. Macromolecules 51, 4003–4011 (2018).

    Article  CAS  Google Scholar 

  179. Wang, H. et al. Chiral, thermal-responsive hydrogels containing helical hydrophilic polyacetylene: preparation and enantio-differentiating release ability. Polym. Chem. 10, 1780–1786 (2019).

    Article  CAS  Google Scholar 

  180. Pijper, D. & Feringa, B. L. Molecular transmission: controlling the twist sense of a helical polymer with a single light-driven molecular motor. Angew. Chem. Int. Ed. 46, 3693–3696 (2007).

    Article  CAS  Google Scholar 

  181. Lotz, B. in Synthesis, Structure and Properties of Poly(lactic acid) (eds Di Lorenzo, M. L. & Androsch, R.) 273–302 (Springer, 2018).

  182. Thomas, S. W., Joly, G. D. & Swager, T. M. Chemical sensors based on amplifying fluorescent conjugated polymers. Chem. Rev. 107, 1339–1386 (2007).

    Article  CAS  PubMed  Google Scholar 

  183. Zhu, C., Liu, L., Yang, Q., Lv, F. & Wang, S. Water-soluble conjugated polymers for imaging, diagnosis, and therapy. Chem. Rev. 112, 4687–4735 (2012).

    Article  CAS  PubMed  Google Scholar 

  184. Liu, B. & Bazan, G. C. (eds) Conjugated Polyelectrolytes: Fundamentals and Applications (Wiley, 2013).

  185. Kane-Maguire, L. A. P. & Wallace, G. G. Chiral conducting polymers. Chem. Soc. Rev. 39, 2545–2576 (2010).

    Article  CAS  PubMed  Google Scholar 

  186. Ho, H.-A., Najari, A. & Leclerc, M. Optical detection of DNA and proteins with cationic polythiophenes. Acc. Chem. Res. 41, 168–178 (2008).

    Article  CAS  PubMed  Google Scholar 

  187. Ho, H. et al. Colorimetric and fluorometric detection of nucleic acids using cationic polythiophene derivatives. Angew. Chem. Int. Ed. 41, 1548–1551 (2002). The demonstration that a helical conformation in conjugated polymers leads to unique spectroscopic responses that can be exploited to sense chemical mutations in DNA.

    Article  CAS  Google Scholar 

  188. Doré, K. et al. Fluorescent polymeric transducer for the rapid, simple, and specific detection of nucleic acids at the zeptomole level. J. Am. Chem. Soc. 126, 4240–4244 (2004).

    Article  PubMed  CAS  Google Scholar 

  189. Ho, H. A. et al. Direct molecular detection of nucleic acids by fluorescence signal amplification. J. Am. Chem. Soc. 127, 12673–12676 (2005).

    Article  CAS  PubMed  Google Scholar 

  190. Nilsson, K. P. R. & Inganäs, O. Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative. Nat. Mater. 2, 419–424 (2003).

    Article  CAS  PubMed  Google Scholar 

  191. Najari, A. et al. Reagentless ultrasensitive specific DNA array detection based on responsive polymeric biochips. Anal. Chem. 78, 7896–7899 (2006).

    Article  CAS  PubMed  Google Scholar 

  192. Fukuhara, G. & Inoue, Y. Highly selective oligosaccharide sensing by a curdlan–polythiophene hybrid. J. Am. Chem. Soc. 133, 768–770 (2011).

    Article  CAS  PubMed  Google Scholar 

  193. Nilsson, K. P. R., Rydberg, J., Baltzer, L. & Inganäs, O. Twisting macromolecular chains: self-assembly of a chiral supermolecule from nonchiral polythiophene polyanions and random-coil synthetic peptides. Proc. Natl Acad. Sci. USA 101, 11197–11202 (2004).

    Article  CAS  PubMed  Google Scholar 

  194. Sigurdson, C. J. et al. Prion strain discrimination using luminescent conjugated polymers. Nat. Methods 4, 1023–1030 (2007).

    Article  CAS  PubMed  Google Scholar 

  195. Lim, E.-K. et al. Nanomaterials for theranostics: recent advances and future challenges. Chem. Rev. 115, 327–394 (2015).

    Article  CAS  PubMed  Google Scholar 

  196. Betts, J. G. et al. in Anatomy and Physiology Ch. 3.1 (OpenStax, 2013).

Download references

Acknowledgements

P.F.-T. thanks the University of Birmingham for the John Evans Fellowship. T.L. gratefully acknowledges financial support from the Engineering and Physical Sciences Research Council (EPSRC) through a studentship from the Centre for Doctoral Training in Physical Sciences for Health (EP/L016346/1).

Author information

Authors and Affiliations

  1. School of Chemistry, University of Birmingham, Edgbaston, Birmingham, UK

    Thomas Leigh & Paco Fernandez-Trillo

Authors
  1. Thomas Leigh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paco Fernandez-Trillo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T.L. and P.F.-T. reviewed the literature, organized the Review and designed the figures. P.F.-T. wrote the manuscript, with both authors contributing to the final version of the Review.

Corresponding author

Correspondence to Paco Fernandez-Trillo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Chemistry thanks C. Scholz, E. Palermo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Secondary structure

The conformational arrangement (α-helix, β-pleated sheet etc.) of the backbone segments of a macromolecule, such as a polypeptide chain of a protein, without regard to the conformation of the side chains or the relationship to other segments.

Helicity

The chirality of a helical, propeller or screw-shaped molecular entity.

Helix

The molecular conformation of a spiral nature, generated by regularly repeating rotations around the backbone bonds of a macromolecule.

Helical sense

The sense of rotation around the helical axis. Viewing from either end of a molecule downwards along the helical axis, the system has P helicity (or plus) if the rotation is clockwise (or right-handed) and M helicity (or minus) if the rotation is anticlockwise (or left-handed).

Drug delivery

The translocation of a therapeutic agent to the site of activity or infection.

Gram-negative bacteria

Bacteria that have a thin peptidoglycan layer and an outer lipid membrane.

Gram-positive bacteria

Bacteria that have a thick peptidoglycan layer and no outer lipid membrane.

Gene delivery

A process by which foreign genetic material, for example, DNA or RNA, is transferred to host cells for applications such as genetic research or gene therapy. Gene delivery can result in multiple effects, including gene knockdown, i.e. the deactivation or suppression of a gene, gene knockin, i.e. the one-for-one substitution of a gene into a host’s genome, or gene knockout, i.e. the total removal or permanent deactivation of a gene.

Gene knockdown

The deactivation or suppression of a gene.

Helical pitch

Also known as (chain) identity period or (chain) conformational repeating unit. The distance or number of residues along the chain axis for a complete turn. This conformational unit is repeated along the chain through symmetry operations. In an α-helix formed from α-amino acids, there are 3.6 residues per ‘turn’, with a 5.4-angstroms turn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leigh, T., Fernandez-Trillo, P. Helical polymers for biological and medical applications. Nat Rev Chem 4, 291–310 (2020). https://doi.org/10.1038/s41570-020-0180-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-020-0180-5

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research