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Analysis of hairpin polyamide complexes having DNA binding sites in close proximity

Hawkins, Cheryl A. and Baird, Eldon E. and Dervan, Peter B. and Wemmer, David E. (2002) Analysis of hairpin polyamide complexes having DNA binding sites in close proximity. Journal of the American Chemical Society, 124 (43). pp. 12689-12696. ISSN 0002-7863. doi:10.1021/ja020335b. https://resolver.caltech.edu/CaltechAUTHORS:20160510-081401405

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Abstract

The binding of two hairpin polyamide ligands at adjacent sites on DNA has been studied using NMR spectroscopy. The ligands ImPyPy-γ-PyPyPy-Gly-Dp and Ac-ImPyPy-γ-PyPyPy-Gly-Dp were studied binding to oligomers containing one or two matched binding sites:  5‘-XGTTA-3‘ and 5‘-TAACX_NGTTA-3‘, where X is G, C, or A and N = 0, 1 or 2. At these sites the C-terminal ring shows an equilibrium between normal and inverted conformations. Better binding was observed with the ligand running 5‘ to 3‘ along the contacted strand than in the opposite direction. Complexes of DNAs with two binding sites indicated that at least one spacing base pair was required, and that the identity of this base pair was not critical. Binding with 5‘ to 3‘ contact is again preferred. Demonstrated binding at adjacent sites indicates that it may be possible to engineer cooperative binding for enhanced specificity or affinity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja020335bDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja020335bPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja020335bPublisherSupporting Information
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2002 American Chemical Society. Received March 4, 2002; Publication Date (Web): October 9, 2002. We thank the National Institutes of Health for grant support (GM43129 to D.E.W. and GM27681 to P.B.D.) and acknowledge instrumentation grants from DOE (DE FG05-86ER75281) and NSF (DMB 86-09305 and BBS 87-20134).
Funders:
Funding AgencyGrant Number
NIHGM-43129
NIHGM-27681
Department of Energy (DOE)DE FG05-86ER75281
NSFDMB 86-09305
NSFBBS 87-20134
Issue or Number:43
DOI:10.1021/ja020335b
Record Number:CaltechAUTHORS:20160510-081401405
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-081401405
Official Citation:Analysis of Hairpin Polyamide Complexes Having DNA Binding Sites in Close Proximity Cheryl A. Hawkins, Eldon E. Baird, Peter B. Dervan, and David E. Wemmer Journal of the American Chemical Society 2002 124 (43), 12689-12696 DOI: 10.1021/ja020335b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66811
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:18 May 2016 16:33
Last Modified:11 Nov 2021 00:03

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