Authors
Zhenquan Sun, Wai Yin Yau, Huajie Kang, Haiyan Zhou, Xin Liu, Zhibo Han, Hongxiang Wu, Xuechen Li
Published in
Science advances. Volume 12. Issue 40. Pages eaej5227. Oct 02, 2026. Epub Sep 30, 2026.
Abstract
Chemical protein synthesis has transformed the preparation of homogeneous peptides and proteins with site-specific modifications. Serine/threonine ligation offers a practical route to access difficult peptides and proteins via its aggregation-breaking intermediate, yet the preparation and regeneration of the prerequisite peptidyl salicylaldehyde ester still require the development of more efficient chemistry. Here, we report a silver(I)-mediated amide-to-ester transformation on unprotected peptides, enabled by an easily introduced N,S-benzylidene thioacetal scaffold. This method can chemoselectively convert backbone amides into salicylaldehyde esters in aqueous acetic acid without detectable epimerization, which is demonstrated by comprehensive syntheses of various peptide examples, the efficient total synthesis of mirror-image histones histone 2A (H2A), H2B, H3, and H4, and detailed mechanistic studies. This strategy establishes a general organic platform for programmable amide activation at the peptide or protein level.
PMID:
42814821
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.
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