Tolman R L, Field A K, Karkas J D, Wagner A F, Germershausen J, Crumpacker C, Scolnick E M
Biochem Biophys Res Commun. 1985 May 16;128(3):1329-35. doi: 10.1016/0006-291x(85)91086-1.
As part of our study of antiherpetic acyclonucleosides, we synthesized a cyclic GMP analog, 9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]guanine P-oxide, sodium salt (2'-nor-cGMP), and discovered its potent and broad spectrum anti-DNA-viral activities. 2'-Nor-cGMP inhibits the replication of many DNA viruses, including herpes simplex virus, human cytomegalovirus, vaccinia, SV40, and adenovirus, but does not inhibit RNA viruses. In plaque reduction studies this potent antiviral agent is also approximately 10-fold more potent than 9-(1,3-dihydroxy-2-propoxymethyl)guanine (2'NDG) against varicella-zoster virus and inhibits cell transformation by bovine papilloma virus. Unlike 2'NDG, the potent activity of 2'-nor-cGMP against herpes virus is not dependent upon the action of virus-specified thymidine kinase. Intercellular metabolism of 2'-nor-cGMP produced small amounts of 2'NDG triphosphate which were insufficient to account for the antiviral activity observed, implying that this potent anti-DNA-viral agent operates by a mechanism different from that of known acyclonucleosides.
作为我们对抗疱疹阿昔洛韦核苷研究的一部分，我们合成了一种环鸟苷酸类似物，即9-[(2-羟基-1,3,2-二氧磷杂环己烷-5-基)氧甲基]鸟嘌呤P-氧化物钠盐（2'-去甲环鸟苷酸），并发现了其强大且广谱的抗DNA病毒活性。2'-去甲环鸟苷酸可抑制多种DNA病毒的复制，包括单纯疱疹病毒、人巨细胞病毒、痘苗病毒、SV40和腺病毒，但不抑制RNA病毒。在蚀斑减少研究中，这种强效抗病毒剂对水痘带状疱疹病毒的效力也比9-(1,3-二羟基-2-丙氧甲基)鸟嘌呤（2'NDG）强约10倍，并且能抑制牛乳头瘤病毒引起的细胞转化。与2'NDG不同，2'-去甲环鸟苷酸对疱疹病毒的强效活性不依赖于病毒特异性胸苷激酶的作用。2'-去甲环鸟苷酸的细胞间代谢产生少量的2'NDG三磷酸，其不足以解释所观察到的抗病毒活性，这意味着这种强效抗DNA病毒剂的作用机制与已知的阿昔洛韦核苷不同。
