(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.

引用

页码：521 / 527

页数：7

共 35 条

[1] STUDY OF THE PLASMA-CLEARANCE OF ANTIBODY RICIN-A-CHAIN IMMUNOTOXINS - EVIDENCE FOR SPECIFIC RECOGNITION SITES ON THE A-CHAIN THAT MEDIATE RAPID CLEARANCE OF THE IMMUNOTOXIN [J].