Energetically Important C鈭扝路路路F鈭扖 Pseudohydrogen Bonding in Water: Evidence and Application to Rational Design of Oligonucleotides with High Binding Affinity

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• 作者：Maryam Yahyaee Anzahaee ; Jonathan K. Watts ; Nageswara R. Alla ; Allen W. Nicholson ; Masad J. Damha
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：February 2, 2011
• 年：2011
• 卷：133
• 期：4
• 页码：728-731
• 全文大小：736K
• 年卷期：v.133,no.4(February 2, 2011)
• ISSN：1520-5126

文摘

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鈥睩-ANA is largely due to a C鈭扝路路路F鈭扖 pseudohydrogen bond at pyrimidine鈭抪urine 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鈥?position. These results provide a rational method to increase the binding affinity of antisense oligonucleotides by placement of 2鈥睩-ANA modifications at pyrimidine鈭抪urine steps.