Solution Structure of a Nonpolar, Non-Hydrogen-Bonded Base Pair Surrogate in DNA

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• 作者：Kevin M. Guckian ; Thomas R. Krugh ; and Eric T. Kool
• 刊名：Journal of the American Chemical Society
• 出版年：2000
• 出版时间：July 26, 2000
• 年：2000
• 卷：122
• 期：29
• 页码：6841 - 6847
• 全文大小：177K
• 年卷期：v.122,no.29(July 26, 2000)
• ISSN：1520-5126

文摘

We describe the structure in aqueous solution of a DNA duplex containing a base pair that isstructurally analogous to A-T but which lacks hydrogen bonds. Base analogues F (a nonpolar isostere ofthymine) and Z (a nonpolar isostere of adenine) are paired opposite one another in a 12 base pair duplex. Thesequence context is the binding site of recently studied transcription factor hSRY. The Z-F pair has beenshown to be replicated surprisingly well and selectively by DNA polymerase enzymes, considering that it isdestabilizing and lacks Watson-Crick hydrogen bonds. The enzymatic studies led to the suggestion that partof the functional activity arises because the pair resembles a natural one in geometry. The present results showthat, despite the absence of Watson-Crick hydrogen bonds, the Z-F pair structurally resembles an A-T pairin the same context. This lends support to the proposal that shape matching is an important component inreplication, and suggests the general utility of using Z-F as a nonpolar replacement for A-T in probingprotein-DNA interactions.