BORONIC ACID INHIBITORS OF BETA-LACTAMASES

β-内酰胺酶是水解β-内酰胺的丝氨酸酶 青霉素和头孢菌素中的环。 他们是主要原因 青霉素耐药性的证据。 与丝氨酸蛋白酶不同， 它们在活性部位没有组氨酸。 作用机制 的行动是没有很好地理解。 我们已经表明，两种内酰胺酶被抑制（微摩尔浓度 Ki's）通过几种硼酸。 在这项研究中，我们将准备 更高特异性的硼酸抑制剂，并研究它们的模式 酶动力学的抑制作用。 的pH依赖性 预期抑制将阐明酰化的机制， 脱酰作用。 我们已经研究了硼酸在抑制 青霉素抗性和细菌生长。 这将继续下去 新的化合物。

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.