(6-MALEIMIDOCAPROYL)HYDRAZONE OF DOXORUBICIN - A NEW DERIVATIVE FOR THE PREPARATION OF IMMUNOCONJUGATES OF DOXORUBICIN

被引：188
作者：
WILLNER, D
TRAIL, PA
HOFSTEAD, SJ
KING, HD
LASCH, SJ
BRASLAWSKY, GR
GREENFIELD, RS
KANEKO, T
FIRESTONE, RA
机构：
[1] Bristol-Myers Squibb Company, Connecticut 06492-7660, 5 Research Parkway, Wallingford
[2] Bristol-Myers Squibb Pharmaceutical Research Institute, NJ 08543., P.O. Box 4000, Princeton
[3] CT 06033, 124 Heritage Drive, Glastonbury
[4] CT 06492, 10 Sieter Hill Rd, Wallingford
[5] Pfizer Central Research, CT 06430, Groton
来源：
BIOCONJUGATE CHEMISTRY | 1993年 / 4卷 / 06期
关键词：
D O I：
10.1021/bc00024a015
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
The (6-maleimidocaproyl)hydrazone of doxorubicin was synthesized and conjugated to several mAbs, including chimeric BR96, via a Michael addition reaction to thiol-containing mAbs. DTT reduction of disulfides present in the mAb was a reliable and general method for generating a consistent number of reactive SH groups. The conjugates, after purification by Bio-Beads, were free of unreacted linker and/or doxorubicin. All conjugates released doxorubicin under acidic conditions that mimic the lysosomal environment, while they were relatively stable at neutral pH. BR96 conjugates showed antigen-specific cytotoxicity.
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页码：521 / 527
页数：7
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