ENZYME-INHIBITORS .26. BRIDGING HYDROPHOBIC AND HYDROPHILIC REGIONS ON ADENOSINE DEAMINASE WITH SOME 9-(2-HYDROXY-3-ALKYL)ADENINES
ENZYME-INHIBITORS .26. BRIDGING HYDROPHOBIC AND HYDROPHILIC REGIONS ON ADENOSINE DEAMINASE WITH SOME 9-(2-HYDROXY-3-ALKYL)ADENINES
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DOI：
10.1021/jm00247a002
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发表时间：
1974-01-01
影响因子：
7.3
通讯作者：
SCHWENDER, CF
中科院分区：
文献类型：
--
作者：
SCHAEFFER, HJ;SCHWENDER, CF
描述了以5-氨基- 4,6 -二氯嘧啶和相应的氨基醇为原料合成红腺嘌呤和三-9-（2-羟基-3-烷基）腺嘌呤。基于早期的研究，预测并证实了红血球非对映异构体比相应的三对映异构体更有效地抑制腺苷脱氨酶。这些数据支持在腺苷脱氨酶上抑制剂的腺嘌呤部分有一个单一的结合位点，并且甲基结合位点、羟基结合位点和抑制剂的9取代基利用的大疏水区域之间存在密切的空间关系。早期的研究表明，犊牛肠黏膜腺苷脱氨酶具有几个对结合各种9-取代腺嘌呤的9取代基很重要的区域。这些9取代基的结合区域是一个大的疏水区，1是羟基结合
The syntheses of some erythro-and threo-9-(2-hydroxy-3-alkyl) adenines from 5-amino-4, 6-dichloropyrimidine and the appropriate amino alcohols are described. Based on earlier studies, it was predicted and substantiated that the erythro diastereoisomers would be more potent inhibitors of adenosine deaminase than their corresponding threo diastereoisomers. These data support the concept that on adenosine deaminase there is a single binding site for the adenine moiety of the inhibitors and that there is a close spatial relationship of the methyl binding site, the hy-droxyl binding site, and thelarge hydrophobic region utilized by the 9 substituent of the inhibitors.Earlier studies have shown that calf intestinal mucosal adenosine deaminase possesses several regions which are important for binding the 9 substituent of various 9-sub-stituted adenines. 1" 3 These binding areas for the 9 sub-stituent are a large hydrophobic region, 1 a hydroxyl bind-