乳清苷5'-单磷酸脱羧酶的抑制作用及其治疗潜力。

Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential.

作者信息

Meza-Avina M E, Wei L, Buhendwa M G, Poduch E, Bello A M, Pai E F, Kotra L P

机构信息

Center for Molecular Design and Preformulations, Toronto General Hopsital, Toronto, Ontario, Canada M5G 2C4, Canada.

出版信息

Mini Rev Med Chem. 2008 Mar;8(3):239-47. doi: 10.2174/138955708783744065.

DOI:10.2174/138955708783744065

PMID:18336344

Abstract

Orotidine 5'-monophosphate decarboxylase (ODCase) is among the most proficient enzymes, and catalyzes the decarboxylation of OMP to UMP. An overview of ODCase and various proposals for its catalytic mechanism of decarboxylation are briefly presented here. A number of inhibitors of ODCase and new developments in the X-ray structures of ODCases from different species are discussed in the context of their therapeutic potential against cancer and infectious diseases. Latest discoveries in the inhibition of ODCase, for example using the novel C6 substitutions on the uridine, open new doors for drug discovery targeting parasitic diseases such as malaria.

摘要

乳清苷5'-单磷酸脱羧酶（ODCase）是最高效的酶之一，催化乳清苷单磷酸（OMP）脱羧生成尿苷单磷酸（UMP）。本文简要概述了ODCase及其脱羧催化机制的各种观点。结合ODCase抑制剂在抗癌和抗传染病方面的治疗潜力，讨论了多种ODCase抑制剂以及不同物种ODCase的X射线结构的新进展。ODCase抑制方面的最新发现，例如在尿苷上使用新型C6取代，为针对疟疾等寄生虫病的药物研发打开了新的大门。