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.
Site-selective modification of cysteine residues is central to the construction of peptide- and protein-based probes and therapeutics, yet existing methods are often constrained by linkage instability, narrow substrate scope, or harsh, nonbiocompatible reaction conditions. Here we report a palladium-catalyzed, site-s...
Quan-Ping Guo, Chun-Lin Wang, Xin Ma et al.· JACS Au· 0 citations
Native chemical ligation (NCL) is a well-established research tool used to access long and complex peptides that cannot be efficiently synthesized by other means such as linear solid-phase peptide synthesis (SPPS). However, its broader application beyond the research laboratory scale has been limited by low-volume yi...
P. H. G. Egelund, Jonathan Pfeuffer-Rooschüz, Sandip Jadhav et al.· JACS Au· 0 citations
Genetically encoded libraries of peptide-derived macrocycles containing electrophile “warheads” (cGELs) can be used to identify potent and selective covalent ligands for protein targets. Such cGELs are synthesized either by incorporation of unnatural amino acids that display mild electrophiles on their side chains or...
James H. Walker, Arunika I. Ekanayake, Nichole J. Pedowitz et al.· Journal of the American Chem...· 0 citations
Glycopeptides are key structural motifs of powerful pharmaceuticals and of relevance for the molecular understanding in the life sciences. Despite major advances, the synthesis of glycopeptides largely relies on prefunctionalized substrates and lengthy synthesis sequences. In sharp contrast, the assembly of diverse g...
Julia Pöhlmann, Adelina Timmann-Kopp, F. Lorenzi et al.· ACS Catalysis· 0 citations
Peptides have broad applications in fields such as food, medicine, and functional materials. Conventional solid-phase peptide synthesis (SPPS) constructs diverse peptide sequences through stepwise amino acid elongation but relies on stoichiometric coupling reagents and organic solvents, thereby generating considerable...
2-Deoxyglycosylamides have great potential for biochemical applications, but their streamlined synthesis remains underexplored. Herein, 2-pentafluorophenylpyridinium tetrafluoroborate was designed for highly stereoselective glycosylation of amides with glycals. Besides the challenging substrates like glucals, the met...
Qin-Bo Jiao, Zhen-Bo Guo, Shuai Jiang et al.· Journal of the American Chem...· 0 citations
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