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. PMCID PMC38666. https://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

Related URLs:

URL	URL Type	Description
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC38666/	PubMed Central	Article
http://www.pnas.org/cgi/content/abstract/93/16/8306	Other	UNSPECIFIED
http://www.pnas.org/cgi/content/abstract/93/16/8306	Other	UNSPECIFIED

ORCID:

Author	ORCID
Dervan, Peter B.	0000-0001-8852-7306

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.

Funders:

Funding Agency	Grant Number
NIH	GM-23509
NIH	GM-34469
NIH	CA-47995
NIH	GM-27681
Howard Hughes Medical Institute (HHMI)	UNSPECIFIED

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

Issue or Number:

PubMed Central ID:

PMC38666

Record Number:

CaltechAUTHORS:PILpnas96

Persistent URL:

https://resolver.caltech.edu/CaltechAUTHORS:PILpnas96

Official Citation:

D S Pilch, N Poklar, C A Gelfand, S M Law, K J Breslauer, E E Baird, and P B Dervan Binding of a hairpin polyamide in the minor groove of DNA: sequence-specific enthalpic discrimination PNAS 1996 93 (16) 8306-8311

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ID Code:

1484

Collection:

CaltechAUTHORS

Deposited By:

Tony Diaz

Deposited On:

23 Jan 2006

Last Modified:

26 Nov 2019 11:15

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