Benzyloxycarbonyl-D-Phe-Pro-methoxypropylboroglycine: a novel inhibitor of thrombin with high selectivity containing a neutral side chain at the P1 position.
Benzyloxycarbonyl-D-Phe-Pro-methoxypropylboroglycine: a novel inhibitor of thrombin with high selectivity containing a neutral side chain at the P1 position.
复制标题
Benzyloxycarbonyl-D-Phe-Pro-methoxyarylboroglycine：一种新型凝血酶抑制剂，具有高选择性，在 P1 位含有中性侧链。
DOI：
10.1042/bj2900309
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
L. Niu
中科院分区：
文献类型：
--
作者：
G. Claeson;M. Philipp;E. Agner;M. Scully;R. Metternich;V. Kakkar;T. DeSoyza;L. Niu
凝血酶（凝血酶）是一种具有胰蛋白酶样特异性的丝氨酸蛋白酶，能够裂解 Arg-Xaa 肽键，但仅限于非常有限数量的底物（及其位点）。对于预防和治疗血栓形成，控制凝血酶活性是一个关键目标，最近已经推出了多种合成抑制剂，它们都在P1位点带有正电荷。我们报告了第一个在 P1 位点含有中性侧链的新型抑制剂的合成，即肽苄氧基羰基-D-Phe-Pro-甲氧基丙基硼甘氨酸。该肽是一种有效的凝血酶抑制剂 [Ki（限制）= 7 nM]，并且相对于其他丝氨酸蛋白酶，对其靶酶具有高度选择性。与传统的带正电荷的抑制剂相比，这有望在作用特异性和降低毒性方面带来相当大的优势。
Thrombin, the blood-clotting enzyme, is a serine proteinase with trypsin-like specificity and is able to cleave Arg-Xaa peptide bonds but only in a very limited number of substrates (and sites therein). For the prevention and treatment of thrombosis the control of thrombin activity is a key target, and a variety of synthetic inhibitors have been introduced recently, all of which have a positive charge at the P1 site. We report the synthesis of the first example of a new class of inhibitor containing a neutral side chain at the P1 site, the peptide benzyloxycarbonyl-D-Phe-Pro- methoxypropylboroglycine. The peptide is a potent inhibitor of thrombin [Ki (limiting) = 7 nM] and is highly selective for its target enzyme in respect of other serine proteinases. This may be expected to confer considerable advantage in terms of specificity of action and reduced toxicity over conventional, positively charged, inhibitors.