N10-substituted 5,8-dideazafolate inhibitors of glycinamide ribonucleotide transformylase.
N10-substituted 5,8-dideazafolate inhibitors of glycinamide ribonucleotide transformylase.
复制标题
甘氨酰胺核糖核苷酸转化酶的 N10 取代 5,8-二脱氮杂叶酸抑制剂。
DOI：
10.1021/jm00390a024
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发表时间：
1987
影响因子：
7.3
通讯作者：
Caperelli,CA
中科院分区：
文献类型：
--
作者：
Caperelli,CA
A series of 5, 8-dideazafolates bearing ethyl, isopropyl, cyclopropylmethyl, propargyl, 3-cyanopropyl, carboxymethyl, 2-carboxyethyl, phenacyl, 3-fluorobenzyl, and 5-uracilylmethyl substituents at N10 were tested as inhibitors of purified L5178Y glycinamide ribonucleotide transformylase (GAR TFase), which requires 10-formyltetrahydrofolate as cofactor. All of these cofactor analogues exhibited competitive inhibition against M-formyl-5, 8-dideazafolate, with Kf s ranging from 2 to 32 µ.We have recently demonstrated that both 5, 8-dideazafolate (1) and the lV10-acetyl (7) analoguecould inhibit the GAR TFase catalyzed formylation of glycinamide ribonucleotide (GAR) by N10-formyl-5, 8-dideazafolate in a competitive manner. 1 This reaction is the first of two folate-dependent formyl group transfers in the de novo purine biosynthetic pathway. Previous studies had indi-cated that the IV^-formyl analogue was utilized very ef-ficiently as a substrate by GAR TFase isolated from both avian2 and mammalian sources3, 4 and that this analogue was very effective as an affinity ligand for enzyme puri-fication. 3, 6
