Acid-cleavable thiomaleamic acid linker for homogeneous antibody-drug conjugation

被引：60

作者：

Castaneda, Lourdes ^{[1
]}

Maruani, Antoine ^{[1
]}

Schumacher, Felix F. ^{[1
]}

Miranda, Enrique ^{[2
]}

Chudasama, Vijay ^{[1
]}

Chester, Kerry A. ^{[2
]}

Baker, James R. ^{[1
]}

Smith, Mark E. B. ^{[1
]}

Caddick, Stephen ^{[1
]}

机构：

[1] UCL, Dept Chem, London WC1H 0AJ, England

[2] UCL Canc Inst, London WC1E 6BT, England

来源：

CHEMICAL COMMUNICATIONS | 2013年 / 49卷 / 74期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

MONOCLONAL-ANTIBODIES; THERAPEUTIC INDEX; BREAST-CANCER; FUTURE; BROMOMALEIMIDES; TRASTUZUMAB; DOXORUBICIN;

D O I：

10.1039/c3cc45220d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In this communication we describe a novel acid-cleavable linker strategy for antibody-drug conjugation. Functional disulfide bridging of the single interchain disulfide bond of a trastuzumab Fab fragment yields a homogeneous antibody-drug conjugate bearing a thiomaleamic acid linker. This linker is stable at physiological pH and temperature, but quantitatively cleaves at lysosomal pH to release the drug payload.

引用

收藏

页码：8187 / 8189

页数：3

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