Department of Chemistry, Savitribai Phule Pune University (SPPU), Pune, Maharashtra, 411007, India.
Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1885-1889. doi: 10.1002/anie.201609733. Epub 2017 Jan 12.
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 NH 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.
马来酰亚胺介导的生物分子的硫醇特异性衍生化是目前最有效的生物缀合方法之一。然而，令人震惊的是，最近的工作表明，所得的硫代马来酰亚胺缀合物容易通过巯基交换反应而分解。在此，我们报告了一类新的马来酰亚胺，即邻-CH2NHPr 苯基马来酰亚胺，它们在与巯基缀合后会经历前所未有的快速环水解，形成稳定的巯基交换抗性缀合物。此外，我们通过开发这种支架的光笼版本来克服由于马来酰亚胺试剂易于在生物缀合之前发生环水解而导致的低货架寿命问题，该光笼版本可以抵抗环水解。用这种光笼化马来酰亚胺形成的巯基生物缀合物经 UV 照射后，可在温和的冰冷条件下在 1 h 内迅速发生硫代马来酰亚胺环水解，生成所需的稳定缀合物。
