A dual-enzyme cleavable linker for antibody-drug conjugates

被引：23

作者：

Bargh, Jonathan D. ^{[1
]}

Walsh, Stephen J. ^{[1
,2
]}

Ashman, Nicola ^{[1
]}

Isidro-Llobet, Albert ^{[3
]}

Carroll, Jason S. ^{[2
]}

Spring, David R. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England

[2] Univ Cambridge, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England

[3] GSK, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

来源：

CHEMICAL COMMUNICATIONS | 2021年 / 57卷 / 28期

基金：

英国工程与自然科学研究理事会;

关键词：

Enzymes;

D O I：

10.1039/d1cc00957e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A novel enzyme cleavable linker for antibody-drug conjugates is reported. The 3-O-sulfo-beta-galactose linker is cleaved sequentially by two lysosomal enzymes - arylsulfatase A and beta-galactosidase - to release the payload in targeted cells. An alpha-HER2 antibody-drug conjugate synthesised using this highly hydrophilic dual-cleavable linker exhibited excellent cytotoxicity and selectivity.

引用

页码：3457 / 3460

页数：4

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