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Stable and Rapid Thiol Bioconjugation by Light‐Triggered Thiomaleimide Ring Hydrolysis
Author(s) -
Kalia Dimpy,
Pawar Sharad P.,
Thopate Jyoti S.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201609733
Subject(s) - bioconjugation , maleimide , thiol , chemistry , hydrolysis , derivatization , biomolecule , combinatorial chemistry , reagent , conjugate , ring (chemistry) , organic chemistry , biochemistry , mathematical analysis , high performance liquid chromatography , mathematics
Maleimide‐mediated thiol‐specific derivatization of biomolecules is one of the most efficacious bioconjugation approaches currently available. Alarmingly, however, recent work demonstrates that the resulting thiomaleimide conjugates are susceptible to breakdown via thiol exchange reactions. Herein, we report a new class of maleimides, namely o ‐CH 2 NH i Pr phenyl maleimides, that undergo unprecedentedly rapid ring hydrolysis after thiol conjugation to form stable thiol exchange‐resistant conjugates. Furthermore, we overcome the problem of low shelf lives of maleimide reagents owing to their propensity to undergo ring hydrolysis prior to bioconjugation by developing a photocaged version of this scaffold that resists ring hydrolysis. UV irradiation of thiol bioconjugates formed with this photocaged maleimide unleashes rapid thiomaleimide ring hydrolysis to yield the desired stable conjugates within 1 h under gentle, ice‐cold conditions.