DIALDEHYDES DERIVED FROM ADENINE NUCLEOSIDES AS SUBSTRATES AND INHIBITORS OF ADENOSINE AMINOHYDROLASE
DIALDEHYDES DERIVED FROM ADENINE NUCLEOSIDES AS SUBSTRATES AND INHIBITORS OF ADENOSINE AMINOHYDROLASE
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DOI：
10.1021/bi00580a025
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发表时间：
1979-01-01
期刊：
影响因子：
2.9
通讯作者：
LERNER, LM
中科院分区：
文献类型：
--
作者：
GRANT, AJ;LERNER, LM
将不同的腺嘌呤核苷用准周期酸处理后，制得一系列核苷二醛粉末。氧化得到由腺苷(1)，9- α衍生的二醛。-d -甘露诺吡喃基腺苷(2),9-(5-脱氧-。- d -阿拉伯糖脲基)腺嘌呤(3),9- α。- l -鼠李糖苷(4),9- β。-L-fucopyranosyladenine(5), 9-。-D-fucopyranosyladenine(6), 9-。- d -阿拉伯吡喃葡萄糖苷(7),9- β。-d -核糖体核苷(8)和9-(5-脱氧-。-D-erythro-pent-4-enofuranosyl)腺嘌呤(9)。核苷二醛1-3和6-8是犊牛肠黏膜腺苷氨基水解酶（EC 3.5.4.4）的弱底物。双醛8亲合力最强，Vmax最大；除5种外，其余二醛均为该酶的抑制剂。最佳抑制剂为9个（Ki = 4 .mu）。M)和4 (Ki = 28 μ M)；它们都不是底物。抑制剂没有表现出时间依赖性的抑制作用，也没有与蛋白质形成共价键。二醛的活性形式显然是开链二水合物。9还原得到的醇是最强的抑制剂（Ki = 0.9 .mu）。M)在相关醇和核苷二醛之间。
A series of nucleoside dialdehydes were obtained as powders after treatment of various adenine nucleosides with paraperiodic acid. Oxidation gave dialdehydes derived from adenosine (1), 9-.alpha.-D-mannopyranosyladenine (2), 9-(5-deoxy-.alpha.-D-arabinofuranosyl)adenine (3), 9-.alpha.-L-rhamnopyranosyladenine (4), 9-.beta.-L-fucopyranosyladenine (5), 9-.beta.-D-fucopyranosyladenine (6), 9-.alpha.-D-arabinopyranosyladenine (7), 9-.beta.-D-ribopyranosyladenine (8) and 9-(5-deoxy-.beta.-D-erythro-pent-4-enofuranosyl)adenine (9). Nucleoside dialdehydes 1-3 and 6-8 were weak substrates for adenosine aminohydrolase (EC 3.5.4.4) from calf intestinal mucosa. Dialdehyde 8 had the strongest affinity, but 1 had the highest Vmax. All dialdehydes except 5 were inhibitors of the enzyme. The best inhibitors were 9 (Ki = 4 .mu.M) and 4 (Ki = 28 .mu.M); neither were substrates. The inhibitors did not exhibit time-dependent inhibition and did not appear to form covalent bonds with the protein. The active forms of the dialdehydes are apparently the open-chain dihydrates. The alcohol obtained by reduction of 9 was the strongest inhibitor (Ki = 0.9 .mu.M) among the related alcohols and the nucleoside dialdehydes.