Acidity of secondary hydroxyls in ATP and adenosine analogues and the question of a 2′,3′-hydrogen bond in ribonucleosides
Acidity of secondary hydroxyls in ATP and adenosine analogues and the question of a 2′,3′-hydrogen bond in ribonucleosides
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DOI：
10.1021/ja0477468
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发表时间：
2004-11-17
影响因子：
15
通讯作者：
Strömberg, R
中科院分区：
文献类型：
--
作者：
Åstrom, H;Limén, E;Strömberg, R
由于糖修饰的核苷、核苷酸和寡核苷酸在药理学和酶学研究中广泛使用，因此有关仲羟基相对 pKa 值的知识对设计和解释有很大帮助。为此，我们测定了水溶液中 ATP、dATP、2'-F-dATP、2'-NH2-ATP 和 2'-O-甲基 ATP 的酸度常数。相对酸度的影响似乎主要来自诱导效应，因为发现 pKa 值和基团电负性之间存在良好的相关性。腺苷中 2’-OH 和 3’-氧阴离子之间的氢键没有明显的能量贡献。为了澄清这种氢键是否会在极性较小的溶剂中做出更突出的能量贡献，我们还测定了水、甲醇和 DMSO 中腺苷、2'-O-甲基腺苷和 3'-O-甲基腺苷中仲羟基的酸度。然而，所有溶剂中 pKa 值的相对差异非常相似，这表明腺苷中的分子内氢键没有产生主要的能量贡献。
As sugar-modified nucleosides, nucleotides, and oligonucleotides are much used in pharmacology and enzymatic studies, knowledge on the relative pKavalues of the secondary hydroxyls can be of great help in design and interpretations. To obtain this, we have determined the acidity constants for ATP, dATP, 2‘-F-dATP, 2‘-NH2-ATP, and 2‘-O-methyl ATP in aqueous solution. The influence of the relative acidities seem to be mainly from inductive effects since a good correlation between pKavalues and group electronegativity is found. There is no clear energetic contribution from a much suggested H-bond between the 2‘-OH and 3‘-oxyanion in adenosine. To clarify if this kind of H-bond would make a more-prominent energetic contribution in less-polar solvents, we also determined the acidity of secondary hydroxyls in adenosine, 2‘-O-methyladenosine, and 3‘-O-methyladenosine in water, methanol, and DMSO. The relative differences in pKavalues were, however, quite similar in all solvents, suggesting that no major energetic contribution is made by an intramolecular H-bond in adenosine.