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Recognition of 5‘-(A,T)GG(A,T)_2-3‘ Sequences in the Minor Groove of DNA by Hairpin Polyamides

Parks, Michelle E. and Baird, Eldon E. and Dervan, Peter B. (1996) Recognition of 5‘-(A,T)GG(A,T)_2-3‘ Sequences in the Minor Groove of DNA by Hairpin Polyamides. Journal of the American Chemical Society, 118 (26). pp. 6153-6159. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-103339578

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Abstract

A series of four hairpin pyrrole−imidazole polyamides, ImImPy-γ-PyPyPy-β-Dp, PyPyPy-γ-ImImPy-β-Dp, AcImImPy-γ-PyPyPy-β-Dp, and AcPyPyPy-γ-ImImPy-β-Dp (Im = N-methylimidazole-2-carboxamide, Py = N-methylpyrrole-2-carboxamide, Dp = N,N-dimethylaminopropylamide, γ = γ-aminobutyric acid, β = β-alanine, and Ac = acetyl), designed for recognition of 5‘-(A,T)GG(A,T)_2-3‘ sequences in the minor groove of DNA were synthesized using solid phase methodology and analyzed with respect to DNA binding affinity and sequence specificity. Quantitative DNase I footprint titration experiments reveal that the optimal polyamide ImImPy-γ-PyPyPy-β-Dp binds a designated 5‘-TGGTT-3‘ match site with an equilibrium association constant of K_a = 1.0 × 10^8 M^(-1) and the single base pair mismatch sites, 5‘-TGTTA-3‘ and 5‘-GGGTA-3‘, with 50-fold and 100-fold-lower affinity, respectively (10 mM Tris·HCl, 10 mM KCl, 10 mM MgCl_2, and 5 mM CaCl_2, pH 7.0 and 22 °C). Polyamides of sequence composition AcImImPy-γ-PyPyPy-β-Dp and AcPyPyPy-γ-ImImPy-β-Dp, which differ only by the position of the γ-linker, bind with similar affinities and specificities. Recognition of sequences containing contiguous G·C base pairs expands the sequence repertoire available for targeting DNA with pyrrole−imidazole polyamides.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja9607289DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja9607289PublisherArticle
Additional Information:© 1996 American Chemical Society. Received March 6, 1996. Publication Date (Web): July 3, 1996. Abstract published in Advance ACS Abstracts, June 15, 1996. Acknowledgment. We are grateful to the National Institutes of Health (GM-27681) for research support, the National Institutes of Health for a research service award to M.E.P., and the Howard Hughes Medical Institute for a predoctoral fellowship to E.E.B.
Funders:
Funding AgencyGrant Number
NIHGM-27681
NIH Predoctoral FellowshipUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:26
Record Number:CaltechAUTHORS:20160510-103339578
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-103339578
Official Citation:Recognition of 5‘-(A,T)GG(A,T)2-3‘ Sequences in the Minor Groove of DNA by Hairpin Polyamides Michelle E. Parks, Eldon E. Baird, and Peter B. Dervan Journal of the American Chemical Society 1996 118 (26), 6153-6159 DOI: 10.1021/ja9607289
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66887
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 22:14
Last Modified:03 Oct 2019 10:01

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