Inhibition of arginine gingipains (RgpB and HRgpA) with benzamidine inhibitors: Zinc increases inhibitory potency
Inhibition of arginine gingipains (RgpB and HRgpA) with benzamidine inhibitors: Zinc increases inhibitory potency
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DOI：
10.1515/bc.2002.131
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发表时间：
2002-07-01
影响因子：
3.7
通讯作者：
Powers, JC
中科院分区：
文献类型：
--
作者：
Krauser, JA;Potempa, J;Powers, JC
我们用HRgpA和RgpB这两种与牙周炎和牙周病发病相关的酶来测试几种联苯胺衍生物的抑制效力。结果表明，苯甲胺类化合物是HRgpA和RgpB的有效抑制剂，最好的抑制剂是带有尿素连接基的双苯甲胺(K-I=30um)。在低浓度锌存在下，含有连接两个芳环的尿素部分的苯甲酰胺类化合物的缓蚀效果提高了2-3倍。我们提出了一个四面体锌原子与牙龈痛的活性部位Cys和His，以及联苯双胺抑制剂中的尿素连接物配位的抑制模型。综上所述，我们发现了一系列新的有效的牙龈痛抑制剂，并找到了一种新的方法来提高使用锌的HRgpA和RgpB牙龈痛的抑制剂效力。
We assayed several benzamidine derivatives for inhibition potency with HRgpA and RgpB gingipains, enzymes which are involved in the pathogenesis of gingivitis and periodontal disease. The benzamidine derivatives proved to be effective inhibitors of HRgpA and RgpB, with the best inhibitor being a bisbenzamidine with a urea linker (K-i=30 muM). The inhibition potency was increased 2-3 fold in the presence of low concentrations of zinc with the benzamidines containing a urea moiety linking the two aromatic rings. We propose an inhibition model involving a tetrahedral zinc atom coordinated with the active site Cys and His of gingipain and the urea linker in the benzamidine inhibitor. In summary, we have discovered a new series of effective inhibitors for the gingipains and found a novel way to increase inhibitor potency with the HRgpA and RgpB gingipains using zinc.