Thiol-Containing Cross-Linking Agent with Enhanced Steric Hindrance

被引：26

作者：

Greenfield, Lawrence ^{[1
]}

Bloch, Will ^{[1
]}

Moreland, Margaret ^{[2
]}

机构：

[1] Cetus Corp, PCR Dept, Emeryville, CA 94608 USA

[2] Cetus Corp, Dept Chem, Emeryville, CA 94608 USA

来源：

BIOCONJUGATE CHEMISTRY | 1990年 / 1卷 / 06期

关键词：

D O I：

10.1021/bc00006a006

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Ricin A chain immunotoxins disulfide cross-linked with conventional, sterically unhindered reagents have unsatisfactorily short circulating life times in vivo. (Acetylthio)succinic anhydride, a thiolating reagent with partial steric hindrance of the sulfur atom, does not remedy this situation. Sulfosuccinimidyl N-[3-(acetylthio)-3-methylbutyryl]-beta-alaninate, a new cross-linker in which the carbon a to the sulfur is doubly methylated, creates disulfide bonds 2 orders of magnitude more resistant to reduction than unhindered disulfides. Nevertheless, this deactivated thiolating agent rapidly and reliably cross-links ricin A chain and antibodies to create immunotoxins with in vitro cytotoxicities comparable to those of 2-iminothiolane-coupled conjugates.

引用

页码：400 / 410

页数：11

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