Use of pKa differences to enhance the formation of base triplets involving C-G and G-C base pairs
Use of pKa differences to enhance the formation of base triplets involving C-G and G-C base pairs
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DOI：
10.1021/jo000754w
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发表时间：
2000-11-03
影响因子：
3.6
通讯作者：
McLaughlin, LW
中科院分区：
文献类型：
--
作者：
Chen, DL;McLaughlin, LW
两个 C-核苷用于识别 dC-dG 碱基对。两种衍生物都与 dC 相关，但缺少 Oa-羰基。羰基的缺失应该消除该位点上任何不利的空间相互作用。其中一种衍生物含有α-氨基吡啶杂环(d2APy)，而第二种衍生物含有2-氨基嘧啶杂环(d2APm)。前者的 pK(a) 为 6.8，在识别 dG-dC 碱基对方面比在与 dC-dG 租约对的结合方面具有更好的功能。 pK(a) 为 3.3 的 d2APm 导数与 dC-dG 碱基对形成碱基三联体的功能优于与 dG-dC 靶标形成碱基三联体的功能。将两种情况下的三倍体 T-m 与包含天然 dC 残基的序列进行比较。 dC 类似物似乎与目标 dG 碱基残基形成两个氢键，其中之一需要环氮的质子化。目标 dC 残基的识别似乎需要与 C-核苷形成单个氢键，并且使氮大部分处于非质子化状态有利于其形成。
Two C-nucleosides are employed for the recognition of dC-dG base pairs. Both derivatives are related to dC but lack, the Oa-carbonyl. The absence of the carbonyl should eliminate any unfavorable steric interactions at this site. One of the derivatives contains a a-aminopyridine heterocycle (d2APy) while the second contains a 2-aminopyrimidine heterocycle (d2APm). The former with a pK(a) of 6.8 functions better for the recognition of dG-dC base pairs than it does in the binding to dC-dG lease pairs. The d2APm derivative with a pK(a) of 3.3 functions better to form base triplets with dC-dG base pairs than with dG-dC targets. Tripler T-m's in both cases are compared with the sequence containing the native dC residue. The dC analogues appear to make two hydrogen bonds to a target dG base residue, one of which requires protonation of the ring nitrogen. Recognition of a target dC residue appears to require the formation of a single hydrogen bond to the C-nucleoside and having that nitrogen largely in the unprotonated state facilitates its formation.