BORONIC ACID INHIBITORS OF BETA-LACTAMASES

β-内酰胺酶是降解β-内酰胺的丝氨酸酶。 加入青霉素和头孢菌素类药物。他们是主要的原因 细菌对青霉素的耐药性。与丝氨酸蛋白酶不同， 他们的活性部位没有组氨酸。他们的机制 对行动的理解还不是很清楚。 我们已经证明了两种内酰胺酶被抑制(与微摩尔 KI‘s)由几种硼酸组成。在这项研究中，我们将准备 更高特异度的硼酸缓蚀剂及其模式研究 使用酶动力学进行抑制。细菌对pH的依赖性 抑制有望阐明酰化和 脱酰化。 我们研究了硼酸的抑制作用。 青霉素耐药与细菌生长这将继续下去 新化合物的作用。

Beta-lactamases are serine enzymes that hydrolyze the beta-lactam ring in penicillins and cephalosporins. They are the main cause of penicillin resistance in bacteria. Unlike serine proteases, they do not have a histidine in the active site. Their mechanism of action is not well-understood. We have shown that two lactamases are inhibited (with micromolar Ki's) by several boronic acids. In this study, we will prepare more highly specific boronic acid inhibitors and study their mode of inhibition using enzyme kinetics. The pH-dependence of inhibition is expected to clarify the mechanism of acylation and deacylation. We have studied the effectiveness of boronic acids in inhibiting penicillin resistance and bacterial growth. This will be continued with the new compounds.