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Published August 6, 1996 | Published
Journal Article Open

Binding of a hairpin polyamide in the minor groove of DNA: Sequence-specific enthalpic discrimination

Abstract

Hairpin polyamides are synthetic ligands for sequence-specific recognition in the mirror groove of double-helical DNA. A thermodynamic characterization of the DNA-binding properties exhibited by a six-sing hairpin polyarmide, ImPyPy-gamma-PyPyPy-beta-Dp (where Im = imidazole, Pv = pyrrole, gamma = gamma-amimobutyric acid, beta = beta-alaniae, and Dp = dimethylaminopropylamide), reveals an approximate to 1-2 kcal/mol greater affinity for the designated match site, 5'-TGTTA-3' relative to the single base pair mismatch sites, 5'-TGGTA-3' and 5'-TATTA-3'. The enathalpy and entropy data at 20 degrees C reveal this sequence specificity to be entirely enthalpic in origin. Correlations between the thermodynamic driving forces underlying the sequence specificity exhibited by Im-PyPy-gamma-PyPyPy-beta-Dp and the structural properties of the heterodimeric complex of PyPyPy and ImPyPy bound to the minor grope of DNA provide insight into the molecular forces that govern the affinity and specificity of pyrrole-imidazole polyamides.

Additional Information

© 1996 by the National Academy of Sciences. Contributed by Peter B. Dervan, May 13, 1996. We thank Dr. Jens Volker for his assistance with the acquisition and analysis of the DSC data. This work was supported by National Institutes of Health Grants GM-23509 (K.J.B.), GM-34469 (K.J.B.), CA-47995 (K.J.B.), and GM-27681 (P.B.D.). We are grateful to the Howard Hughes Medical Institute for a Predoctoral Fellowship to E.E.B. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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August 22, 2023
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