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. doi:10.1021/ja9607289. https://resolver.caltech.edu/CaltechAUTHORS:20160510-103339578
Full text is not posted in this repository. Consult Related URLs below.
Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20160510-103339578
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: |
| |||||||||
| ORCID: |
| |||||||||
| 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: |
| |||||||||
| Issue or Number: | 26 | |||||||||
| DOI: | 10.1021/ja9607289 | |||||||||
| 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: | 11 Nov 2021 00:23 |
Repository Staff Only: item control page
