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

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	A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates
	Ding Wei1,2,3 ; Yurong Mao2,3 ; Huihui Wang2,3 ; Siqi Qu2,3 ; Jiakang Chen2 ; Jiusheng Li 1; Biao Jiang2 ; Hongli Chen2
	2022-12-23
发表期刊	CHINESE CHEMICAL LETTERS (IF:9.4[JCR-2023],7.3[5-Year])
ISSN	1001-8417
发表状态	已发表
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 IC50. 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)
收录类别	SCI
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/290005
专题	免疫化学研究所免疫化学研究所_特聘教授组_抗体化学实验室免疫化学研究所_公共科研平台_分析化学平台生命科学与技术学院_硕士生物质科学与技术学院_硕士生
共同第一作者	Yurong Mao
通讯作者	Jiusheng Li; Biao Jiang; Hongli Chen
作者单位	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
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Ding Wei,Yurong Mao,Huihui Wang,et al. A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates[J]. CHINESE CHEMICAL LETTERS,2022.
APA	Ding Wei.,Yurong Mao.,Huihui Wang.,Siqi Qu.,Jiakang Chen.,...&Hongli Chen.(2022).A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates.CHINESE CHEMICAL LETTERS.
MLA	Ding Wei,et al."A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates".CHINESE CHEMICAL LETTERS (2022).