Controlling Binding Orientation in Hairpin Polyamide DNA Complexes
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- 作者：Cheryl A. Hawkins ; Rafael Pelá ; ez de Clairac ; Raymond N. Dominey ; Eldon E. Baird ; Sarah White ; Peter B. Dervan ; and David E. Wemmer
- 刊名：Journal of the American Chemical Society
- 出版年：2000
- 出版时间：June 7, 2000
- 年：2000
- 卷：122
- 期：22
- 页码：5235 - 5243
- 全文大小：421K
- 年卷期：v.122,no.22(June 7, 2000)
- ISSN：1520-5126
文摘
The effects of N-terminal acetylation and C-terminal tail structure on the orientation of binding ofimidazole/pyrrole polyamide DNA ligands has been investigated. We find that N-terminal acetylation leads toan intramolecular steric clash for hairpin ligands bound in the minor groove, promoting a rotation of thespatially close C-terminal pyrrole ring. This in turn leads to loss of contacts between the tail and the groove,removing the preference for 5'-to-3' orientational binding typical of this class of ligand. Similarly, introductionof a glycine linker into the tail leads to a direct steric clash with the groove, again promoting rotation of theattached ligand ring. The effects of acetylation and a glycine in the tail are additive. The implications for thedesign of sequence-specific ligands are discussed.