Runge M S, Bode C, Matsueda G R, Haber E
Massachusetts General Hospital, Boston.
Biochemistry. 1988 Feb 23;27(4):1153-7. doi: 10.1021/bi00404a012.
Tissue plasminogen activator (tPA) was covalently linked by disulfide bonds to a monoclonal antibody specific for the amino terminus of the beta chain of fibrin (antibody 59D8). The activity of the tPA-59D8 conjugate was compared with that of tPA, urokinase (UK), and a UK-59D8 conjugate. For lysis of fibrin monomer, tPA was 10 times as potent as UK, whereas both UK-59D8 and tPA-59D8 conjugates were 100 times as potent as UK and 10 times as potent as tPA. Conjugation of tPA or UK to antibody 59D8 produced a 3.2-4.5-fold enhancement in clot lysis in human plasma over that of the respective unconjugated plasminogen activator. However, the UK-59D8 conjugate was only as potent as tPA alone. Antibody-conjugated tPA or UK consumed less fibrinogen, alpha 2-antiplasmin, and plasminogen than did the unconjugated activators, at equipotent fibrinolytic concentrations. Antibody targeting thus appears to increase the concentration of tPA in the vicinity of a fibrin deposit, which thereby leads to enhanced fibrinolysis.
组织型纤溶酶原激活剂（tPA）通过二硫键与针对纤维蛋白β链氨基末端的单克隆抗体（抗体59D8）共价连接。将tPA - 59D8偶联物的活性与tPA、尿激酶（UK）和UK - 59D8偶联物的活性进行了比较。对于纤维蛋白单体的溶解，tPA的效力是UK的10倍，而UK - 59D8和tPA - 59D8偶联物的效力都是UK的100倍，是tPA的10倍。将tPA或UK与抗体59D8偶联，在人血浆中产生的凝块溶解作用比各自未偶联的纤溶酶原激活剂增强了3.2 - 4.5倍。然而，UK - 59D8偶联物的效力仅与单独的tPA相当。在等效的纤维蛋白溶解浓度下，抗体偶联的tPA或UK比未偶联的激活剂消耗的纤维蛋白原、α2 - 抗纤溶酶和纤溶酶原更少。因此，抗体靶向似乎增加了纤维蛋白沉积物附近tPA的浓度，从而导致纤维蛋白溶解增强。
