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Updated: Oct 2, 2026

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
Published on: August 1, 2018
Silver(I)-mediated amide-to-ester transformation on unprotected peptides for protein chemical synthesis and
Zhenquan Sun1, Wai Yin Yau2,3, Huajie Kang2,3
1Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.
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.
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