Department of Pharmaceutical Chemistry, University of Kansas, 2093 Constant Avenue, Lawrence, KS 66047, USA.
Molecules. 2019 Nov 28;24(23):4357. doi: 10.3390/molecules24234357.
Free radical pathways play a major role in the degradation of protein pharmaceuticals. Inspired by biochemical reactions carried out by thiyl radicals in various enzymatic processes, this review focuses on the role of thiyl radicals in pharmaceutical protein degradation through hydrogen atom transfer, electron transfer, and addition reactions. These processes can lead to the epimerization of amino acids, as well as the formation of various cleavage products and cross-links. Examples are presented for human insulin, human and mouse growth hormone, and monoclonal antibodies.
自由基途径在蛋白质药物的降解中起着重要作用。受各种酶促反应中硫自由基引发的生化反应的启发，本综述重点讨论了硫自由基通过氢原子转移、电子转移和加成反应在药物蛋白降解中的作用。这些过程可导致氨基酸的差向异构化，以及形成各种断裂产物和交联产物。以人胰岛素、人源和鼠源生长激素以及单克隆抗体为例进行了说明。
