Cytidine deaminase inhibitors

胞苷对底物构象选择性的研究 与腺苷脱氨酶（ADA）相比， 根据糖的起皱现象解释的酶之间的重要差异 以及核糖氧在结合和催化中的作用（Nucleosides Nucleotides &Nucleic Acids 2009，28，614-632）。在一项使用最有效的CDA抑制剂的研究中， 我们的实验室在80年代的十年里开发了一种二氮杂卓核苷，核糖环， 用双环[3.1.0]己烷模板构建的构象锁定的假糖取代。 利用碳环部分的稳定性， 发现了与母体二氮杂卓酮核苷几乎相等的效力（J.Org.Chem.2009 in Press）。

A study concerning the substrate conformational preferences displayed by cytidine deaminase (CDA) versus the mechanistically similar enzyme, adenosine deaminase (ADA), revealed important differences between the enzymes that were explained on the basis of sugar puckering and the role of the ribose oxygen in binding and catalysis (Nucleosides Nucleotides & Nucleic Acids 2009, 28, 614-632). In a study using the most potent CDA inhibitor that our lab developed in the decade of the 80s, a diazepinone riboside, the ribose ring was replaced with conformationally locked pseudosugars built with a bicyclo[3.1.0]hexane template. Taking advantage of the stability of the carbocyclic moiety a very stable CDA inhibitor that almost equal in potency the parent diazepinone riboside was disovered (J. Org. Chem. 2009 in press).