Cerda Matthew M, Newton Turner D, Zhao Yu, Collins Brylee K, Hendon Christopher H, Pluth Michael D
Department of Chemistry and Biochemistry , Materials Science Institute , Institute of Molecular Biology , University of Oregon , Eugene , Oregon 97403 , USA . Email:
Chem Sci. 2018 Nov 30;10(6):1773-1779. doi: 10.1039/c8sc04683b. eCollection 2019 Feb 14.
Dithioesters have a rich history in polymer chemistry for RAFT polymerizations and are readily accessible through different synthetic methods. Here we demonstrate that the dithioester functional group is a tunable motif that releases HS upon reaction with cysteine and that structural and electronic modifications enable the rate of cysteine-mediated HS release to be modified. In addition, we use (bis)phenyl dithioester to carry out kinetic and mechanistic investigations, which demonstrate that the initial attack by cysteine is the rate-limiting step of the reaction. These insights are further supported by complementary DFT calculations. We anticipate that the results from these investigations will allow for the further development of dithioesters as important chemical motifs for studying HS chemical biology.
二硫酯在用于可逆加成-断裂链转移（RAFT）聚合的聚合物化学中有着丰富的历史，并且可以通过不同的合成方法轻松获得。在这里，我们证明二硫酯官能团是一个可调节的基团，它在与半胱氨酸反应时会释放出HS，并且结构和电子修饰能够改变半胱氨酸介导的HS释放速率。此外，我们使用（双）苯基二硫酯进行动力学和机理研究，结果表明半胱氨酸的初始攻击是该反应的限速步骤。这些见解得到了互补的密度泛函理论（DFT）计算的进一步支持。我们预计，这些研究结果将有助于二硫酯作为研究HS化学生物学的重要化学基团得到进一步发展。
