Mukhametova L I, Aĭsina R B, Lomakina G Iu, Varfolomeev S D
Chemical Faculty, Moscow State University, Vorob'evy gory, Moscow, 119899 Russia.
Bioorg Khim. 2002 Jul-Aug;28(4):308-14.
A chemical modification of single-chain urokinase-type plasminogen activator (scu-PA) with phenylglyoxal under mild conditions resulted in the scu-PA derivatives with various numbers of the modified Arg residues. The study of properties of the resulting derivatives demonstrated that the modification of 4-12 Arg residues did not cause any loss of the activator, fibrinolytic, and potential amidase activities of the activator. The scu-PA with four modified Arg residues was found to be the most stable derivative in human blood plasma; it causes a more efficient lysis of plasma clots than the native activator. Three of four modified Arg residues are supposed to be within the 178RRHRGGS184 cluster, which was localized in the superficial loop of the scu-PA globule and was shown to interact with the complementary series of negatively charged residues in the molecule of the main plasma inhibitor PAI-1. The neutralization of positively charged Arg residues in this cluster decreases the affinity of scu-PA and the double chain urokinase-type plasminogen activator for PAI-1, which results in an enhancement of the stability in plasma and the fibrinolytic efficiency of the activator. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.
在温和条件下用苯乙二醛对单链尿激酶型纤溶酶原激活剂（scu-PA）进行化学修饰，得到了具有不同数量修饰精氨酸（Arg）残基的scu-PA衍生物。对所得衍生物性质的研究表明，修饰4 - 12个Arg残基不会导致激活剂的激活、纤维蛋白溶解及潜在酰胺酶活性丧失。发现具有四个修饰Arg残基的scu-PA是在人血浆中最稳定的衍生物；它比天然激活剂能更有效地溶解血浆凝块。四个修饰的Arg残基中有三个推测位于178RRHRGGS184簇内，该簇位于scu-PA球状体的表面环中，并已证明其与主要血浆抑制剂PAI-1分子中带负电荷的互补序列相互作用。该簇中带正电荷的Arg残基被中和会降低scu-PA和双链尿激酶型纤溶酶原激活剂对PAI-1的亲和力，这导致激活剂在血浆中的稳定性增强以及纤维蛋白溶解效率提高。论文英文版本：《俄罗斯生物有机化学杂志》，2002年，第28卷，第4期；另见http://www.maik.ru 。
