一种单一酶对一种广谱抗病毒药物的激活与失活作用：腺苷脱氨酶催化两个连续的脱氨反应。
Activation and deactivation of a broad-spectrum antiviral drug by a single enzyme: adenosine deaminase catalyzes two consecutive deamination reactions.
作者信息
Wu Jim Zhen, Walker Heli, Lau Johnson Y N, Hong Zhi
机构信息
Research & Development, Ribapharm Corporation, Costa Mesa, California 92626, USA.
出版信息
Antimicrob Agents Chemother. 2003 Jan;47(1):426-31. doi: 10.1128/AAC.47.1.426-431.2003.
Abstract
Ribavirin is an approved broad-spectrum antiviral drug. A liver-targeting prodrug of ribavirin, viramidine, is in clinical trial in an attempt to provide a better therapeutic index. The conversion of viramidine to ribavirin, and of ribavirin to an inactive metabolite through adenosine deaminase, is reported. Kinetic analysis indicates that adenosine deaminase is likely involved in activation of viramidine in vivo, and the process is highly pH sensitive. The differential activities of two consecutive deamination reactions are kinetically studied and interpreted based on adenosine deaminase structural information. A comprehensive understanding of the viramidine and ribavirin deamination mechanism should help in designing better nucleoside therapeutics in the future.
摘要
利巴韦林是一种已获批准的广谱抗病毒药物。利巴韦林的肝脏靶向性前药——维拉美定，正在进行临床试验，以期提供更好的治疗指数。据报道，维拉美定可转化为利巴韦林，且利巴韦林可通过腺苷脱氨酶转化为无活性代谢物。动力学分析表明，腺苷脱氨酶可能参与维拉美定在体内的激活过程，且该过程对pH高度敏感。基于腺苷脱氨酶的结构信息，对两个连续脱氨反应的差异活性进行了动力学研究和解释。全面了解维拉美定和利巴韦林的脱氨机制，应有助于未来设计出更好的核苷类治疗药物。
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