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Fast and Tight Boronate Formation for Click Bioorthogonal Conjugation
Author(s) -
Akgun Burcin,
Hall Dennis G.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201510321
Subject(s) - bioorthogonal chemistry , chemistry , click chemistry , boronic acid , combinatorial chemistry , mass spectrometry , maleimide , nuclear magnetic resonance spectroscopy , thioredoxin , chromatography , organic chemistry , enzyme
A new click bioorthogonal reaction system was devised to enable the fast ligation ( k ON ≈340 m −1 s −1 ) of conjugatable derivatives of a rigid cyclic diol (nopoldiol) and a carefully optimized boronic acid partner, 2‐methyl‐5‐carboxymethylphenylboronic acid. Using NMR and fluorescence spectroscopy studies, the corresponding boronates were found to form reversibly within minutes at low micromolar concentration in water, providing submicromolar equilibrium constant ( K eq ≈10 5 –10 6 m −1 ). Efficient protein conjugation under physiological conditions was demonstrated with model proteins thioredoxin and albumin, and characterized by mass spectrometry and gel electrophoresis.