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Proteomimetics as protein-inspired scaffolds with defined tertiary folding patterns

Nature Chemistry volume 12, pages 331–337 (2020)Cite this article

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Abstract

Proteins have evolved as a variable platform that provides access to molecules with diverse shapes, sizes and functions. These features have inspired chemists for decades to seek artificial mimetics of proteins with improved or novel properties. Such work has focused primarily on small protein fragments, often isolated secondary structures; however, there has lately been a growing interest in the design of artificial molecules that mimic larger, more complex tertiary folds. In this Perspective, we define these agents as ‘proteomimetics’ and discuss the recent advances in the field. Proteomimetics can be divided into three categories: protein domains with side-chain functionality that alters the native linear-chain topology; protein domains in which the chemical composition of the polypeptide backbone has been partially altered; and protein-like folded architectures that are composed entirely of non-natural monomer units. We give an overview of these proteomimetic approaches and outline remaining challenges facing the field.

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Fig. 1: Overview of protein structures and their mimetics.
Fig. 2: Examples of proteomimetics based on altered chain topology.
Fig. 3: Examples of proteomimetics based on partially artificial backbone compositions.
Fig. 4: Examples of proteomimetics based on entirely artificial backbone compositions.

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References

  1. Sali, A., Shakhnovich, E. & Karplus, M. How does a protein fold? Nature 369, 248–251 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Gante, J. Peptidomimetics — tailored enzyme inhibitors. Angew. Chem. Int. Ed. 33, 1699–1720 (1994).

    Article  Google Scholar 

  3. Pelay-Gimeno, M., Glas, A., Koch, O. & Grossmann, T. N. Structure-based design of inhibitors of protein–protein interactions: mimicking peptide binding epitopes. Angew. Chem. Int. Ed. 54, 8896–8927 (2015).

    Article  CAS  Google Scholar 

  4. Clercq, E. D. The design of drugs for HIV and HCV. Nat. Rev. Drug. Discov. 6, 1001–1018 (2007).

    Article  PubMed  CAS  Google Scholar 

  5. Azzarito, V., Long, K., Murphy, N. S. & Wilson, A. J. Inhibition of α-helix-mediated protein–protein interactions using designed molecules. Nat. Chem. 5, 161–173 (2013).

    Article  CAS  PubMed  Google Scholar 

  6. Robertson, N. S. & Spring, D. R. Using peptidomimetics and constrained peptides as valuable tools for inhibiting protein–protein interactions. Molecules 23, 959 (2018).

    Article  PubMed Central  CAS  Google Scholar 

  7. Scott, D. E., Bayly, A. R., Abell, C. & Skidmore, J. Small molecules, big targets: drug discovery faces the protein–protein interaction challenge. Nat. Rev. Drug. Discov. 15, 533–550 (2016).

    Article  CAS  PubMed  Google Scholar 

  8. Kent, S. B. H. Novel protein science enabled by total chemical synthesis. Protein Sci. 28, 313–328 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Krall, N., da Cruz, F. P., Boutureira, O. & Bernardes, G. J. L. Site-selective protein-modification chemistry for basic biology and drug development. Nat. Chem. 8, 102–112 (2016).

    Article  CAS  Google Scholar 

  10. Renata, H., Wang, Z. J. & Arnold, F. H. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution. Angew. Chem. Int. Ed. 54, 3351–3367 (2015).

    Article  CAS  Google Scholar 

  11. Huang, P. S., Boyken, S. E. & Baker, D. The coming of age of de novo protein design. Nature 537, 320–327 (2016).

    Article  CAS  PubMed  Google Scholar 

  12. Chin, J. W. Expanding and reprogramming the genetic code. Nature 550, 53–60 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. Orner, B. P., Ernst, J. T. & Hamilton, A. D. Toward proteomimetics: terphenyl derivatives as structural and functional mimics of extended regions of an α-helix. J. Am. Chem. Soc. 123, 5382–5383 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Rennie, Y. K., McIntyre, P. J., Akindele, T., Bayliss, R. & Jamieson, A. G. A TPX2 proteomimetic has enhanced affinity for Aurora-A due to hydrocarbon stapling of a helix. ACS Chem. Biol. 11, 3383–3390 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Dombkowski, A. A., Sultana, K. Z. & Craig, D. B. Protein disulfide engineering. FEBS Lett. 588, 206–212 (2014).

    Article  CAS  PubMed  Google Scholar 

  16. Marfey, P. S., Nowak, H., Uziel, M. & Yphantis, D. A. Reaction of bovine pancreatic ribonuclease A with 1,5-difluoro-2,4-dinitrobenzene. J. Biol. Chem. 240, 3264–3269 (1965).

    CAS  PubMed  Google Scholar 

  17. Hartman, F. C. & Wold, F. Bifunctional reagents. Cross-linking of pancreatic ribonuclease with a diimido ester. J. Am. Chem. Soc. 88, 3890–3891 (1966).

    Article  CAS  Google Scholar 

  18. Uy, R. & Wold, F. in Protein Crosslinking: Biochemical and Molecular Aspects (ed. Friedman, M.) 169–186 (Springer, 1977).

  19. Lin, S. H., Konishi, Y., Denton, M. E. & Scheraga, H. A. Influence of an extrinsic cross-link on the folding pathway of ribonuclease A. Conformational and thermodynamic analysis of cross-linked (lysine7-lysine41)-ribonuclease A. Biochemistry 23, 5504–5512 (1984).

    Article  CAS  PubMed  Google Scholar 

  20. Luhmann, T., Mong, S. K., Simon, M. D., Meinel, L. & Pentelute, B. L. A perfluoroaromatic abiotic analog of H2 relaxin enabled by rapid flow-based peptide synthesis. Org. Biomol. Chem. 14, 3345–3349 (2016).

    Article  CAS  PubMed  Google Scholar 

  21. Martinez-Saez, N. et al. Oxetane grafts installed site-selectively on native disulfides to enhance protein stability and activity in vivo. Angew. Chem. Int. Ed. 56, 14963–14967 (2017).

    Article  CAS  Google Scholar 

  22. Ekblad, T. et al. Synthesis and chemoselective intramolecular crosslinking of a HER2-binding affibody. Biopolymers 92, 116–123 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Lindgren, J. & Karlstrom, A. E. Intramolecular thioether crosslinking of therapeutic proteins to increase proteolytic stability. ChemBioChem 15, 2132–2138 (2014).

    Article  CAS  PubMed  Google Scholar 

  24. Moore, E. J., Zorine, D., Hansen, W. A., Khare, S. D. & Fasan, R. Enzyme stabilization via computationally guided protein stapling. Proc. Natl Acad. Sci. USA 114, 12472–12477 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pelay-Gimeno, M., Bange, T., Hennig, S. & Grossmann, T. N. In situ cyclization of native proteins: structure-based design of a bicyclic enzyme. Angew. Chem. Int. Ed. 57, 11164–11170 (2018).

    Article  CAS  Google Scholar 

  26. Robinson, J. A. β-hairpin peptidomimetics: design, structures and biological activities. Acc. Chem. Res. 41, 1278–1288 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Xiao, Q. et al. Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect. Org. Biomol. Chem. 16, 8933–8939 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mutter, M. et al. Template-assembled synthetic proteins with 4-helix-bundle topology. Total chemical synthesis and conformational studies. J. Am. Chem. Soc. 114, 1463–1470 (1992).

    Article  CAS  Google Scholar 

  29. Sasaki, T. & Kaiser, E. T. Synthesis and structural stability of helichrome as an artificial hemeproteins. Biopolymers 29, 79–88 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Lupas, A. N. & Bassler, J. Coiled coils — a model system for the 21st century. Trends Biochem. Sci. 42, 130–140 (2017).

    Article  CAS  PubMed  Google Scholar 

  31. Beesley, J. L. & Woolfson, D. N. The de novo design of α-helical peptides for supramolecular self-assembly. Curr. Opin. Biotechnol. 58, 175–182 (2019).

    Article  CAS  PubMed  Google Scholar 

  32. Wuo, M. G., Hong, S. H., Singh, A. & Arora, P. S. Synthetic control of tertiary helical structures in short peptides. J. Am. Chem. Soc. 140, 16284–16290 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wuo, M. G., Mahon, A. B. & Arora, P. S. An effective strategy for stabilizing minimal coiled coil mimetics. J. Am. Chem. Soc. 137, 11618–11621 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang, C. et al. Site-specific isopeptide bridge tethering of chimeric gp41 N-terminal heptad repeat helical trimers for the treatment of HIV-1 infection. Sci. Rep. 6, 32161 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Timmerman, P., Beld, J., Puijk, W. C. & Meloen, R. H. Rapid and quantitative cyclization of multiple peptide loops onto synthetic scaffolds for structural mimicry of protein surfaces. ChemBioChem 6, 821–824 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Heinis, C. & Winter, G. Encoded libraries of chemically modified peptides. Curr. Opin. Chem. Biol. 26, 89–98 (2015).

    Article  CAS  PubMed  Google Scholar 

  37. Dang, B. B. et al. De novo design of covalently constrained mesosize protein scaffolds with unique tertiary structures. Proc. Natl Acad. Sci. USA 114, 10852–10857 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mueller, C. & Grossmann, T. N. Coiled-coil peptide beacon: a tunable conformational switch for protein detection. Angew. Chem. Int. Ed. 57, 17079–17083 (2018).

    Article  CAS  Google Scholar 

  39. Lou, C. G. et al. Peptide-oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic. Nat. Commun. 7, 12294 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hill, D. J., Mio, M. J., Prince, R. B., Hughes, T. S. & Moore, J. S. A field guide to foldamers. Chem. Rev. 101, 3893–4012 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Bautista, A. D., Craig, C. J., Harker, E. A. & Schepartz, A. Sophistication of foldamer form and function in vitro and in vivo. Curr. Opin. Chem. Biol. 11, 685–692 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goodman, C. M., Choi, S., Shandler, S. & DeGrado, W. F. Foldamers as versatile frameworks for the design and evolution of function. Nat. Chem. Biol. 3, 252–262 (2007).

    Article  CAS  PubMed  Google Scholar 

  43. Gellman, S. H. Foldamers: a manifesto. Acc. Chem. Res. 31, 173–180 (1998).

    Article  CAS  Google Scholar 

  44. Rajarathnam, K. et al. Neutrophil activation by monomeric interleukin-8. Science 264, 90–92 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Chapman, E., Thorson, J. S. & Schultz, P. G. Mutational analysis of backbone hydrogen bonds in staphylococcal nuclease. J. Am. Chem. Soc. 119, 7151–7152 (1997).

    Article  CAS  Google Scholar 

  46. Lu, W., Qasim, M. A., Laskowski, M. & Kent, S. B. H. Probing intermolecular main chain hydrogen bonding in serine proteinase–protein inhibitor complexes: chemical synthesis of backbone-engineered turkey ovomucoid third domain. Biochemistry 36, 673–679 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Beligere, G. S. & Dawson, P. E. Design, synthesis, and characterization of 4-ester CI2, a model for backbone hydrogen bonding in protein α-helices. J. Am. Chem. Soc. 122, 12079–12082 (2000).

    Article  CAS  Google Scholar 

  48. Wales, T. E. & Fitzgerald, M. C. The energetic contribution of backbone–backbone hydrogen bonds to the thermodynamic stability of a hyperstable P22 Arc repressor mutant. J. Am. Chem. Soc. 123, 7709–7710 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Deechongkit, S. et al. Context-dependent contributions of backbone hydrogen bonding to β-sheet folding energetics. Nature 430, 101–105 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Baca, M., Kent, S. B. H. & Alewood, P. F. Structural engineering of the HIV-1 protease molecule with a β-turn mimic of fixed geometry. Protein Sci. 2, 1085–1091 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Jean, F. et al. Synthesis and structural and functional evaluation of a protein modified with a β-turn mimic. J. Am. Chem. Soc. 120, 6076–6083 (1998).

    Article  CAS  Google Scholar 

  52. Viles, J. H. et al. Design, synthesis and structure of a zinc finger with an artificial β-turn. J. Mol. Biol. 279, 973–986 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Kaul, R., Angeles, A. R., Jäger, M., Powers, E. T. & Kelly, J. W. Incorporating β-turns and a turn mimetic out of context in loop 1 of the WW domain affords cooperatively folded β-sheets. J. Am. Chem. Soc. 123, 5206–5212 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Arnold, U. et al. Protein prosthesis: a semisynthetic enzyme with a β-peptide reverse turn. J. Am. Chem. Soc. 124, 8522–8523 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Schmidtgall, B. et al. Dissecting mechanism of coupled folding and binding of an intrinsically disordered protein by chemical synthesis of conformationally constrained analogues. Chem. Commun. 53, 7369–7372 (2017).

    Article  CAS  Google Scholar 

  56. David, R. et al. Artificial chemokines: combining chemistry and molecular biology for the elucidation of interleukin-8 functionality. J. Am. Chem. Soc. 130, 15311–15317 (2008).

    Article  CAS  PubMed  Google Scholar 

  57. Burslem, G. M. et al. Towards “bionic” proteins: replacement of continuous sequences from HIF-1α with proteomimetics to create functional p300 binding HIF-1α mimics. Chem. Commun. 52, 5421–5424 (2016).

    Article  CAS  Google Scholar 

  58. Lombardo, C. M. et al. Design and structure determination of a composite zinc finger containing a nonpeptide foldamer helical domain. J. Am. Chem. Soc. 141, 2516–2525 (2019).

    Article  CAS  PubMed  Google Scholar 

  59. Lee, B.-C. & Zuckermann, R. N. Protein side-chain translocation mutagenesis via incorporation of peptoid residues. ACS Chem. Biol. 6, 1367–1374 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Mayer, C., Müller, M. M., Gellman, S. H. & Hilvert, D. Building proficient enzymes with foldamer prostheses. Angew. Chem. Int. Ed. 53, 6978–6981 (2014).

    Article  CAS  Google Scholar 

  61. Hegedüs, Z. et al. Foldameric α/β-peptide analogs of the β-sheet-forming antiangiogenic anginex: structure and bioactivity. J. Am. Chem. Soc. 135, 16578–16584 (2013).

    Article  PubMed  CAS  Google Scholar 

  62. Cheng, P.-N., Liu, C., Zhao, M., Eisenberg, D. & Nowick, J. S. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. Nat. Chem. 4, 927–933 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Kar, K. et al. β-Hairpin-mediated nucleation of polyglutamine amyloid formation. J. Mol. Biol. 425, 1183–1197 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kar, K. et al. Backbone engineering within a latent β-hairpin structure to design inhibitors of polyglutamine amyloid formation. J. Mol. Biol. 429, 308–323 (2017).

    Article  CAS  PubMed  Google Scholar 

  65. Kreutzer, A. G. & Nowick, J. S. Elucidating the structures of amyloid oligomers with macrocyclic β-hairpin peptides: insights into Alzheimer’s disease and other amyloid diseases. Acc. Chem. Res. 51, 706–718 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Green, B. R. et al. Conotoxins containing nonnatural backbone spacers: cladistic-based design, chemical synthesis, and improved analgesic activity. Chem. Biol. 14, 399–407 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Mong, S. K. et al. Heterochiral knottin protein: folding and solution structure. Biochemistry 56, 5720–5725 (2017).

    Article  CAS  PubMed  Google Scholar 

  68. Haase, H. S. et al. Extending foldamer design beyond α-helix mimicry: α/β-peptide inhibitors of vascular endothelial growth factor signaling. J. Am. Chem. Soc. 134, 7652–7655 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Reinert, Z. E., Lengyel, G. A. & Horne, W. S. Protein-like tertiary folding behavior from heterogeneous backbones. J. Am. Chem. Soc. 135, 12528–12531 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. George, K. L. & Horne, W. S. Foldamer tertiary structure through sequence-guided protein backbone alteration. Acc. Chem. Res. 51, 1220–1228 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. George, K. L. & Horne, W. S. Heterogeneous-backbone foldamer mimics of zinc finger tertiary structure. J. Am. Chem. Soc. 139, 7931–7938 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Checco, J. W. et al. Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold. Proc. Natl Acad. Sci. USA 112, 4552–4557 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Werner, H. M., Estabrooks, S. K., Preston, G. M., Brodsky, J. L. & Horne, W. S. Exploring the functional consequences of protein backbone alteration in ubiquitin through native chemical ligation. ChemBioChem 20, 7752–7755 (2019).

    Article  CAS  Google Scholar 

  74. Cabalteja, C. C., Mihalko, D. S. & Horne, W. S. Heterogeneous-backbone foldamer mimics of a computationally designed, disulfide-rich miniprotein. ChemBioChem 20, 103–110 (2019).

    Article  CAS  PubMed  Google Scholar 

  75. Guichard, G. & Huc, I. Synthetic foldamers. Chem. Commun. 47, 5933–5941 (2011).

    Article  CAS  Google Scholar 

  76. Daniels, D. S., Petersson, E. J., Qiu, J. X. & Schepartz, A. High-resolution structure of a β-peptide bundle. J. Am. Chem. Soc. 129, 1532–1533 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Collie, G. W. et al. Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation. Nat. Chem. 7, 871–878 (2015).

    Article  CAS  PubMed  Google Scholar 

  78. Miller, J. P., Melicher, M. S. & Schepartz, A. Positive allostery in metal ion binding by a cooperatively folded β-peptide bundle. J. Am. Chem. Soc. 136, 14726–14729 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang, P. S. P., Nguyen, J. B. & Schepartz, A. Design and high-resolution structure of a β3-peptide bundle catalyst. J. Am. Chem. Soc. 136, 6810–6813 (2014).

    Article  CAS  PubMed  Google Scholar 

  80. Bécart, D. et al. Helical oligourea foldamers as powerful hydrogen bonding catalysts for enantioselective C–C bond-forming reactions. J. Am. Chem. Soc. 139, 12524–12532 (2017).

    Article  PubMed  CAS  Google Scholar 

  81. Collie, G. W. et al. Molecular recognition within the cavity of a foldamer helix bundle: encapsulation of primary alcohols in aqueous conditions. J. Am. Chem. Soc. 139, 6128–6137 (2017).

    Article  CAS  PubMed  Google Scholar 

  82. Lee, B.-C., Zuckermann, R. N. & Dill, K. A. Folding a nonbiological polymer into a compact multihelical structure. J. Am. Chem. Soc. 127, 10999–11009 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Chandramouli, N. et al. Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose. Nat. Chem. 7, 334–341 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. De, S. et al. Designing cooperatively folded abiotic uni- and multimolecular helix bundles. Nat. Chem. 10, 51–57 (2018).

    Article  CAS  PubMed  Google Scholar 

  85. Lamouroux, A. et al. Controlling dipole orientation through curvature: aromatic foldamer bent β-sheets and helix–sheet–helix architectures. J. Am. Chem. Soc. 139, 14668–14675 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Atcher, J. et al. Aromatic β-sheet foldamers based on tertiary squaramides. Chem. Commun. 55, 10392–10395 (2019).

    Article  CAS  Google Scholar 

  87. Mazzier, D., De, S., Wicher, B., Maurizot, V. & Huc, I. Interplay of secondary and tertiary folding in abiotic foldamers. Chem. Sci. 10, 6984–6991 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hayashi, T., Hilvert, D. & Green, A. P. Engineered metalloenzymes with non-canonical coordination environments. Chem. Eur. J. 24, 11821–11830 (2018).

    Article  CAS  PubMed  Google Scholar 

  89. Schwizer, F. et al. Artificial metalloenzymes: reaction scope and optimization strategies. Chem. Rev. 118, 142–231 (2018).

    Article  CAS  PubMed  Google Scholar 

  90. Lee, H. S. & Schultz, P. G. Biosynthesis of a site-specific DNA cleaving protein. J. Am. Chem. Soc. 130, 13194–13195 (2008).

    Article  CAS  PubMed  Google Scholar 

  91. Drienovská, I., Rioz-Martínez, A., Draksharapu, A. & Roelfes, G. Novel artificial metalloenzymes by in vivo incorporation of metal-binding unnatural amino acids. Chem. Sci. 6, 770–776 (2015).

    Article  PubMed  CAS  Google Scholar 

  92. Drienovská, I. et al. Design of an enantioselective artificial metallo-hydratase enzyme containing an unnatural metal-binding amino acid. Chem. Sci. 8, 7228–7235 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Obexer, R. et al. Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase. Nat. Chem. 9, 50–56 (2016).

    Article  PubMed  CAS  Google Scholar 

  94. Spencer, R. K., Li, H. & Nowick, J. S. X-ray crystallographic structures of trimers and higher-order oligomeric assemblies of a peptide derived from Aβ17–36. J. Am. Chem. Soc. 136, 5595–5598 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank P. Arora and B. Pentelute for providing coordinates of proteomimetic structures from their published work. T.N.G. is grateful for support by the European Research Council (ERC starting grant number 678623). W.S.H. thanks the National Institutes of Health (GM107161) for financial support.

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  1. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA

    W. Seth Horne

  2. Department of Chemistry and Pharmaceutical Sciences, VU University Amsterdam, Amsterdam, the Netherlands

    Tom N. Grossmann

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W.S.H. and T.N.G developed the concept, researched and wrote the manuscript.

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Correspondence to W. Seth Horne or Tom N. Grossmann.

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T.N.G. is listed as an inventor on a patent application related to the INCYPRO stabilization approach.

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Horne, W.S., Grossmann, T.N. Proteomimetics as protein-inspired scaffolds with defined tertiary folding patterns. Nat. Chem. 12, 331–337 (2020). https://doi.org/10.1038/s41557-020-0420-9

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