Introducing Regioselective Disulfide Linkages in Peptides under Pseudodilute Conditions by Harnessing Bronsted Acid-Activated N-Chlorosuccinimide.

ABSTRACT: Methods that assemble multiple peptide disulfide bonds in the solid phase (pseudodilute conditions) are in high demand for synthesizing disulfide-rich peptides. Yet, the existing repertoire of disulfide-forming orthogonal chemistries in the solid phase is often hindered by additional steps for protecting group removals as well as the absolute necessity of rare, customized orthogonal cysteine (Cys) building blocks. We now describe a conceptually new while operationally simple on-resin method for disulfide assembly with widely accessible Cys protecting groups (Trt, Acm, and ^t Bu) using acid-activated N-chlorosuccinimide (NCS) in a single step. In the process, S- ^t Bu Cys emerged as a new orthogonal building block for the single-step assembly of the peptide

SUBMITTER: Tripathi NM 

PROVIDER: S-EPMC11862937 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature