In vitro display evolution of unnatural peptides spontaneously cyclized via intramolecular nucleophilic aromatic substitutions

Chem Commun (Camb). 2022 Apr 26;58(34):5237-5240. doi: 10.1039/d2cc00584k.

Abstract

We report novel, ribosomally incorporatable, and intramolecularly cysteine-reactive fluorobenzoic acid-derived linkers for SELEX of mRNA-displayed unnatural peptides, which spontaneously cyclized via intramolecular nucleophilic aromatic substitutions forming thioethers. With this strategy we identified several novel PCSK9-binding peptides.

MeSH terms

  • Cysteine / chemistry
  • Peptides* / chemistry
  • Peptides, Cyclic / chemistry
  • Proprotein Convertase 9*
  • RNA, Messenger

Substances

  • Peptides
  • Peptides, Cyclic
  • RNA, Messenger
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Cysteine