STRUCTURE ACTIVITY RELATIONSHIP OF PYRIMIDINE BASE ANALOGS AS LIGANDS OF OROTATE PHOSPHORIBOSYLTRANSFERASE
STRUCTURE ACTIVITY RELATIONSHIP OF PYRIMIDINE BASE ANALOGS AS LIGANDS OF OROTATE PHOSPHORIBOSYLTRANSFERASE
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DOI：
10.1016/0006-2952(84)90710-x
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发表时间：
1984-01-01
影响因子：
5.8
通讯作者：
CHA, S
中科院分区：
文献类型：
--
作者：
NIEDZWICKI, JG;ILTZSCH, MH;CHA, S
Eighty pyrimidine base analogs were evaluated as inhibitors of mouse liver orotate phosphoribosyltransferase (OPRTase, EC 2.4.2.10). Based on these findings and an extensive literature review, a structure-activity relationship was formulated for the binding of pyrimidine base analogs to OPRTase. This study provides a basis for the rational design of new inhibitors of this enzyme, and several such compounds are proposed. Additionally, 4,6-dihydroxypyrimidine was found to be a potent OPRTase inhibitor. OPRTase inhibitors were also evaluated as inhibitors of orotidine 5''-monophosphate decarboxylase (ODCase, EC 4.1.1.23). 5-Azauracil, 5-azaorotate and barbituric acid inhibited ODCase significantly only after preincubation with PRPP and MgCl2 in the presence of cytosol.
