Frank K B, Cheng Y C
J Biol Chem. 1986 Feb 5;261(4):1510-3.
Purine ribonucleoside monophosphates were found to inhibit chain elongation catalyzed by herpes simplex virus (HSV) DNA polymerase when DNA template-primer concentrations were rate-limiting. Inhibition was fully competitive with DNA template-primer during chain elongation; however, DNA polymerase-associated exonuclease activity was inhibited noncompetitively with respect to DNA. Combinations of 5'-GMP and phosphonoformate were kinetically mutually exclusive in dual inhibitor studies. Pyrimidine nucleoside monophosphates and deoxynucleoside monophosphates were less inhibitory than purine riboside monophosphates. The monophosphates of 9-beta-D-arabinofuranosyladenine, Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), 9-(2-hydroxyethoxymethyl)guanine, and 9-(1,3-dihydroxy-2-propoxymethyl)guanine exerted little or no inhibition. In contrast to HSV DNA polymerase, human DNA polymerase alpha was not inhibited by purine ribonucleoside monophosphates. These studies suggest the possibility of a physiological role of purine ribonucleoside monophosphates as regulators of herpesvirus DNA synthesis and a new approach to developing selective anti-herpesvirus compounds.
当DNA模板 - 引物浓度成为限速因素时，发现嘌呤核糖核苷单磷酸可抑制单纯疱疹病毒（HSV）DNA聚合酶催化的链延伸。在链延伸过程中，这种抑制作用与DNA模板 - 引物完全竞争；然而，DNA聚合酶相关的核酸外切酶活性对DNA的抑制是非竞争性的。在双重抑制剂研究中，5'-GMP和膦甲酸的组合在动力学上相互排斥。嘧啶核苷单磷酸和脱氧核苷单磷酸的抑制作用比嘌呤核糖核苷单磷酸弱。9-β-D-阿拉伯呋喃糖基腺嘌呤、病毒唑（1-β-D-呋喃核糖基-1,2,4-三唑-3-甲酰胺）、9-(2-羟基乙氧基甲基)鸟嘌呤和9-(1,3-二羟基-2-丙氧基甲基)鸟嘌呤的单磷酸几乎没有抑制作用。与HSV DNA聚合酶不同，人DNA聚合酶α不受嘌呤核糖核苷单磷酸的抑制。这些研究表明嘌呤核糖核苷单磷酸作为疱疹病毒DNA合成调节剂具有生理作用的可能性，以及开发选择性抗疱疹病毒化合物的新方法。
