Sheid B, Gaetjens E, Chung S T, Lerner L M
Department of Pharmacology, SUNY, Health Science Center at Brooklyn 11203, USA.
Experientia. 1996 Sep 15;52(9):878-81. doi: 10.1007/BF01938874.
Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication. To acquire a broad spectrum of new candidate inosine analogues, a rapid, facile, quantitative and stereoselective method for deaminating potential antitumor and antiviral adenine analogues previously synthesized in our laboratory was developed. A novel 5'-adenylic acid deaminase, with relaxed substrate requirements, from Aspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehydes to their corresponding inosine analogues. The fastest rates of deamination for the hexofuranosyl nucleosides were for the compounds where the vicinal hydroxyl groups on the sugars are oriented in the erythro configuration. For rapid deamination of the adenine nucleoside dialdehydes, the R configuration at the proximal carbon atom is preferred, while the nature of the group on the distal carbon atom has no significant effect on the rate or extent of deamination.
从理论上讲，肌苷类似物应可作为肿瘤细胞增殖和病毒复制的有效抑制剂。为了获得一系列新的候选肌苷类似物，我们开发了一种快速、简便、定量且立体选择性的方法，用于对我们实验室之前合成的潜在抗肿瘤和抗病毒腺嘌呤类似物进行脱氨反应。利用一种来自曲霉菌属的新型5'-腺苷酸脱氨酶，该酶对底物的要求较为宽松，将四种己糖呋喃糖基腺嘌呤核苷和五种腺嘌呤核苷二醛脱氨转化为相应的肌苷类似物。己糖呋喃糖基核苷脱氨反应最快的速率出现在糖上邻位羟基呈赤藓糖构型的化合物中。对于腺嘌呤核苷二醛的快速脱氨反应，近端碳原子上的R构型较为有利，而远端碳原子上基团的性质对脱氨反应的速率或程度没有显著影响。
