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A Naturally Encoded Dipeptide Handle for Bioorthogonal Chan–Lam Coupling
Author(s) -
Ohata Jun,
Zeng Yimeng,
Segatori Laura,
Ball Zachary T.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201800828
Subject(s) - bioorthogonal chemistry , bioconjugation , dipeptide , chemistry , combinatorial chemistry , residue (chemistry) , amide , stereochemistry , peptide , biochemistry , click chemistry
Abstract Manipulation of biomacromolecules is ideally achieved through unique and bioorthogonal chemical reactions of genetically encoded, naturally occurring functional groups. The toolkit of methods for site‐specific conjugation is limited by selectivity concerns and a dearth of naturally occurring functional groups with orthogonal reactivity. We report that pyroglutamate amide N−H bonds exhibit bioorthogonal copper‐catalyzed Chan–Lam coupling at pyroglutamate‐histidine dipeptide sequences. The pyroglutamate residue is readily incorporated into proteins of interest by natural enzymatic pathways, allowing specific bioconjugation at a minimalist dipeptide tag.