A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates  

作　　者：Ding Wei Yurong Mao Huihui Wang Siqi Qu Jiakang Chen Jiusheng Li Biao Jiang Hongli Chen 

机构地区：[1]Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China [2]Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai 201210,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Chinese Chemical Letters》2023年第5期494-498,共5页中国化学快报（英文版）

基　　金：supported by Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University。

摘　　要：Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.

关 键 词：Antibody-drug conjugates Self-immolative release Phenoxysilyl linker Combretastatin A4(CA4) 

分 类 号：TQ460.1[化学工程—制药化工]