A BISPECIFIC ANTIBODY ENHANCES THE FIBRINOLYTIC POTENCY OF SINGLE-CHAIN UROKINASE

被引:19
作者
CHARPIE, JR
RUNGE, MS
MATSUEDA, GR
HABER, E
机构
[1] MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
D O I
10.1021/bi00479a005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A monoclonal antibody specific for an epitope at the amino terminus of the β chain of fibrin and a monoclonal antibody that binds both one- and two-chain high molecular weight urokinase were chemically cross-linked [using N-succinimidyl 3-(2-pyridyldithio)propionate and 2-iminothiolane]. The chemically modified material was heterogeneous, ranging in molecular size from tetramers to monomers and containing the two antibodies in various ratios. Nevertheless, fractions of a molecular size larger than a monomer were capable of binding fibrin and urokinase simultaneously in a radioimmunoassay. These fractions also enhanced fibrinolysis by high molecular weight single-chain urokinase (scuPA) by 50-fold and plasma clot lysis by 5-fold. Whereas scuPA significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, scuPA in association with the bispecific antibody did not. © 1990, American Chemical Society. All rights reserved.
引用
收藏
页码:6374 / 6378
页数:5
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