Cys-Lys stapling for unprotected peptides via tunable linkers.

ABSTRACT: Stapling has emerged as a transformative paradigm in peptide chemistry, enabling precise conformational control to endow peptides with augmented biophysical properties, including enhanced proteolytic stability and target-binding affinity. Although symmetric macrocyclization strategies have been investigated, non-symmetric stapling of native peptide scaffolds remains underexplored, owing to intricate synthetic challenges associated with achieving concurrent chemoselectivity and site selectivity. This limitation primarily stems from the requirement for orthogonal reactivity in modifying distinct proteinogenic residues while preserving native side-chain functionalities under biocompatible conditions. Herein, a non-symmetric stapling is disclosed for cysteine-lysine (Cys-Lys) crosslinking in u

SUBMITTER: Miao K 

PROVIDER: S-EPMC12596731 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature