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Titolo:
DESIGN AND EVALUATION OF A THROMBIN-ACTIVABLE PLASMINOGEN-ACTIVATOR
Autore:
YANG WP; GOLDSTEIN J; PROCYK R; MATSUEDA GR; SHAW SY;
Indirizzi:
BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MACROMOLEC BIOCHEM,POB 4000 PRINCETON NJ 08543 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MACROMOLEC BIOCHEM PRINCETON NJ 08543
Titolo Testata:
Biochemistry
fascicolo: 8, volume: 33, anno: 1994,
pagine: 2306 - 2312
SICI:
0006-2960(1994)33:8<2306:DAEOAT>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC AGENTS; FIBRIN; UROKINASE; INACTIVATION; THERAPY; THROMBOMODULIN; MULTICENTER; CLEAVAGE; EFFICACY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
W.P. Yang et al., "DESIGN AND EVALUATION OF A THROMBIN-ACTIVABLE PLASMINOGEN-ACTIVATOR", Biochemistry, 33(8), 1994, pp. 2306-2312

Abstract

A new chimeric plasminogen activator with high fibrin affinity was designed to bind fibrin and to initiate clot destruction, following activation by thrombin. The chimeric activator, 59D8-scuPA-T, was made from the Fab fragment of an anti-fibrin antibody (59D8) and a C-terminal portion of a thromb-inactivable low molecular weight single-chain urokinase plasminogen activator, scuPA-T, obtained by deletion of Phe-157 and Lys-158 from low molecular weight single-chain urokinase-type plasminogen activator (scuPA) by site-directed mutagenesis. The chimeric molecule had a molecular mass of 91000, a value consistent with one 59D8 light chain (M(r) 27000) and one 59D8 heavy-chain Fd fragment fused to low molecular weight scuPA (M(r) = 64000). According to its design,59D8-scuPA-T was activated by thrombin but not by plasmin, whereas the control chimeric molecule, 59D8-scuPA, was activated by plasmin but not by thrombin. When activated by thrombin, 59D8-scuPA-T converted plasminogen to plasmin. In vitro plasma clot lysis assays showed that 59D8-scuPA-T lysed clots preformed by thrombin and that heparin and hirudin could prevent clot lysis. When incorporated as part of a thrombin-induced clot, only 59D8-scuPA-T was able to lyse the clot while 59D8-scuPA and high molecular weight scuPA were ineffective. Together these results demonstrate that 59D8-scuPA-T is a thrombin-activable plasminogen activator that offers selective thrombolysis of thrombin-rich clots over more established, aged clots, and may also act as an antithrombotic agent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:42:13