biostudies-literatureUnknown6(1)Yang YGlycopeptides and glycoproteins with structural precision are valuable for functional studies and applications. Conventional couplings of glycosyl amino acids are slow, wasteful, and impractical for broad use. To address the fundamental synthetic challenges, the current work presents a new paradigm for glycopeptide synthesis, featuring a key component (thioester-functionalized glycosyl amino acid) and a comprehensive reaction system (AgSbF₆ for activation, Oxyma as an additive, DIPEA as a base, under microwave irradiation). The reaction offers rapid and clean on-resin conversion (10 min), economical reagent use (1 equiv), broad effectiveness across varied glycan structures and multiple peptide coupling sites (27 examples), and readiness to automation. Moreover, it seamlessly intJACS Au319-330https://www.ebi.ac.uk/biostudies/studies/S-EPMC12848699biostudies-literatureMicrowave-Assisted Thioester-Empowered Toolkit for Modular Glycopeptide Synthesis.PMC12848699Wang NLi YYang YLi TSchmidt RRPeng PLou HZhang MHao HXiang MHfalseMicrowave-Assisted Thioester-Empowered Toolkit for Modular Glycopeptide Synthesis.Glycopeptides and glycoproteins with structural precision are valuable for functional studies and applications. Conventional couplings of glycosyl amino acids are slow, wasteful, and impractical for broad use. To address the fundamental synthetic challenges, the current work presents a new paradigm for glycopeptide synthesis, featuring a key component (thioester-functionalized glycosyl amino acid) and a comprehensive reaction system (AgSbF₆ for activation, Oxyma as an additive, DIPEA as a base, under microwave irradiation). The reaction offers rapid and clean on-resin conversion (10 min), economical reagent use (1 equiv), broad effectiveness across varied glycan structures and multiple peptide coupling sites (27 examples), and readiness to automation. Moreover, it seamlessly int2026-01-01T00:00:00Z2026 Jan2026-06-17T06:59:11.757Z2026-06-17T03:10:12.019ZS-EPMC128486994161417510.1021/jacsau.5c01264