Energetically Important C-H•••F-C Pseudohydrogen Bonding in Water: Evidence and Application to Rational Design of Oligonucleotides with High Binding Affinity
Energetically Important C-H•••F-C Pseudohydrogen Bonding in Water: Evidence and Application to Rational Design of Oligonucleotides with High Binding Affinity
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DOI：
10.1021/ja109817p
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发表时间：
2011-02-02
影响因子：
15
通讯作者：
Damha, Masad J.
中科院分区：
文献类型：
--
作者：
Anzahaee, Maryam Yahyaee;Watts, Jonathan K.;Damha, Masad J.
有机氟是否能在水环境中形成重要的氢键是有争议的。我们先前通过NMR和分子模拟表明，2 'F-ANA出乎意料的高结合亲和力主要是由于嘧啶嘌呤步骤处的C-H中心点中心点F-C假氢键。具有相同的序列组成，但重排序列的双链体的熔化的比较证实，在这些序列中，在能量上重要的氟介导的假氢键是在操作中。当氢键供体（嘌呤H8）被其自身2 '位上的氟激活时，该效应特别重要。这些结果提供了一个合理的方法，以增加结合亲和力的反义寡核苷酸的2 'F-ANA修饰的嘧啶嘌呤步骤。
It is controversial whether organic fluorine can form energetically important hydrogen bonds in aqueous environments. We previously showed by NMR and molecular modeling that the unexpectedly high binding affinity of 2'F-ANA is largely due to a C-H center dot center dot center dot F-C pseudohydrogen bond at pyrimidine purine steps. Comparisons of the melting of duplexes with identical sequence composition but a rearranged sequence confirm that energetically important fluorine-mediated pseudohydrogen bonding is in operation in these sequences. The effect is of particular importance when the H-bond donor (purine H8) is activated by the presence of fluorine at its own 2'-position. These results provide a rational method to increase the binding affinity of antisense oligonucleotides by placement of 2'F-ANA modifications at pyrimidine purine steps.