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Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally Simple, Rigid Linkers.

ABSTRACT: Copper-mediated coupling between alkynes to generate a structurally rigid, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement to simultaneously maintain CuI and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from CuII -mediated oxidative damage through the formation of an insoluble CuII gel which solves the critical challenge of applying Glaser coupling to substrates that are degraded by CuII . The generality of this method is illustrated through the conjugation of a series of polar and nonpolar labels onto a fully unprotected GLP-1R agonist through a linear 7?Å diynyl linker.

SUBMITTER: Silvestri AP

PROVIDER: S-EPMC5708120 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Adapting the Glaser Reaction for Bioconjugation: Robust Access to Structurally Simple, Rigid Linkers.

Silvestri Anthony P AP Cistrone Philip A PA Dawson Philip E PE

Angewandte Chemie (International ed. in English) 20170721 35

Copper-mediated coupling between alkynes to generate a structurally rigid, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement to simultaneously maintain Cu<sup>I</sup> and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from Cu<sup>II</sup> -mediated oxidative damage through the formation of an insoluble Cu< ...[more]

PMID: 28685936

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