Highly Pure Combinatorial Peptide Libraries by Resin-Enabled Catch and Release.

ABSTRACT: For peptide-drug conjugate (PDC) development, high-quality peptide ligands with easy functionalization are essential. Combinatorial chemical peptide libraries are key for discovering high-affinity non-natural ligands, yet their utility has long been hindered by low-purity libraries that cause false positives. To address this, we developed an N-terminal cysteine-based dynamic catch-and-release (CbDCR) platform, leveraging its unique 1,2-aminothiol motif as a privileged handle for site-selective orthogonal conjugation, enabling efficient library purification while retaining a universal anchor for downstream functionalization. A recyclable 2-formylphenylboronic acid resin (2FPBA resin) was designed to catch and release N-terminal cysteine-containing peptides in a pH-responsive manner, elimina

SUBMITTER: Zuo Q 

PROVIDER: S-EPMC12848724 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature