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

Pilch, Daniel S. and Poklar, Natasa and Gelfand, Craig A. and Law, Scott M. and Breslauer, Kenneth J. and Baird, Eldon E. and Dervan, Peter B. (1996) Binding of a hairpin polyamide in the minor groove of DNA: Sequence-specific enthalpic discrimination. Proceedings of the National Academy of Sciences of the United States of America, 93 (16). pp. 8306-8311. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:PILpnas96

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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.


Item Type:Article
Additional Information:Copyright © 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.
Subject Keywords:polyamide-DNA binding affinity; isothermal calorimetry; 2:1 pyrrole-imidazole DNA binding motif; polyamide-base hydrogen bonds; imidazole-guanine interaction; double-helical DNA; equilibrium melting curves; thermodynamic data; 2-dimensional NMR; netropsin binding; distamycin; recognition; transitions; complexes; motif
Record Number:CaltechAUTHORS:PILpnas96
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:PILpnas96
Alternative URL:http://www.pnas.org/cgi/content/abstract/93/16/8306
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1484
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Jan 2006
Last Modified:14 Nov 2014 19:18

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