核糖基C-3位修饰的底物类似物对S-核糖基高半胱氨酸酶（LuxS）的抑制作用。
Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position.
作者信息
Wnuk Stanislaw F, Robert Jenay, Sobczak Adam J, Meyers Brandon P, Malladi Venkata L A, Zhu Jinge, Gopishetty Bhaskar, Pei Dehua
机构信息
Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA.
出版信息
Bioorg Med Chem. 2009 Sep 15;17(18):6699-706. doi: 10.1016/j.bmc.2009.07.057. Epub 2009 Jul 26.
Abstract
S-ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether bond of S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), which is the precursor of type 2 autoinducer for bacterial cell-cell communication. In this work, we have synthesized several SRH analogues modified at the ribose C3 position as potential inhibitors of LuxS. While removal or methylation of the C3-OH resulted in simple competitive inhibitors of moderate potency, inversion of the C3 stereochemistry or substitution of fluorine for C3-OH resulted in slow-binding inhibitors of improved potency. The most potent inhibitor showed a K(I)(*) value of 0.43 microM.
摘要
S-核糖基高半胱氨酸酶（LuxS）催化S-核糖基高半胱氨酸（SRH）的硫醚键断裂，生成高半胱氨酸和4,5-二羟基-2,3-戊二酮（DPD），DPD是细菌细胞间通讯中2型自诱导物的前体。在本研究中，我们合成了几种在核糖C3位修饰的SRH类似物，作为LuxS的潜在抑制剂。虽然C3-OH的去除或甲基化产生了中等效力的简单竞争性抑制剂，但C3立体化学的反转或用氟取代C3-OH产生了效力提高的慢结合抑制剂。最有效的抑制剂的K(I)(*)值为0.43微摩尔。
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