Jump to main content
Jump to site search


De novo design of constrained and sequence-independent peptide scaffolds with topologically-formidable disulfide connectivities

Author affiliations

Abstract

Disulfide-rich peptides are interesting scaffolds for drug design and discovery. However, peptide scaffolds constrained by disulfide bonds, either naturally occurring or computationally designed, have been suffering from the elusive (oxidative) folding behavior complying with Anfinsen's dogma, which strongly restricts their applicability in bioactive peptide design and discovery; because when primary peptide sequences are extensively manipulated, their disulfide connectivities might become scrambled. Here we present the design of cysteine/penicillamine (C/Pen)-mixed peptide frameworks that are capable of folding into specific regioisomers without dependence on primary amino acid sequences. Even certain folds that are considered to be topologically formidable can be generated in high yields. Currently, almost all disulfide-rich peptide scaffolds are vitally correlated to primary amino acid sequences, but ours are exceptional. These scaffolds should be of particular interest for further designing constrained peptides with new structures and functions, and more importantly, the ultimately designed peptides would not suffer from general oxidative folding problems.

Graphical abstract: De novo design of constrained and sequence-independent peptide scaffolds with topologically-formidable disulfide connectivities

Back to tab navigation

Supplementary files

Publication details

The article was received on 09 Sep 2017, accepted on 17 Nov 2017 and first published on 20 Nov 2017


Article type: Edge Article
DOI: 10.1039/C7SC03956E
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY license
  •   Request permissions

    De novo design of constrained and sequence-independent peptide scaffolds with topologically-formidable disulfide connectivities

    Y. Zheng, X. Meng, Y. Wu, Y. Zhao and C. Wu, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C7SC03956E

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements