RaPID discovery of cell-permeable helical peptide inhibitors con-taining cyclic β-amino acids against SARS-CoV-2 main protease.

ABSTRACT: Structurally constrained cyclic β-amino acids are attractive building blocks for peptide drugs because they induce unique and stable conformations. Introduction of (1S,2S)-2-aminocyclopentanecarboxylic acid [(1S,2S)-2-ACPC] into peptides stabilizes helical conformations, so improving proteolytic stability and cell membrane permeability. We report on the ribosomal synthesis of a helical peptide library incorporating (1S,2S)-2-ACPC at every third position and its application for the discovery of SARS-CoV-2 main protease (M^pro) inhibitors. We identified two peptide sequences containing multiple (1S,2S)-2-ACPC residues, which exhibit helical conformations and superior proteolytic stability compared with their α-Ala or β-Ala cou

SUBMITTER: Kawai M 

PROVIDER: S-EPMC12093385 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature