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

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

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC5869988 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature