ArticleJACS Au2026
Tetrazine-Enabled Peptide Macrocyclization and Bioorthogonal Cell Penetration Profiling.
Article in JACS Au, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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13 authors.
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Abstract
Cyclization of linear peptides into macrocyclic structures confers superior properties such as improved membrane permeability and proteolytic stability while maintaining high target affinity and specificity toward protein targets. Here, we present a cysteine-selective macrocyclization strategy that employs an alkylating motif of chloroethyl tetrazine to react with the thiol side chain in unprotected peptides. This approach efficiently yields cyclic peptides bearing bioorthogonal tetrazine handles, enabling precise late-stage modification via robust tetrazine ligations. We applied this method to synthesize and screen rofapitide tetraxetan analogues, identifying a novel peptide
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