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Kinetic consequences of covalent linkage of DNA binding polyamides

Baliga, Ramesh and Baird, Eldon E. and Herman, David M. and Melander, Christian and Dervan, Peter B. and Crothers, Donald M. (2001) Kinetic consequences of covalent linkage of DNA binding polyamides. Biochemistry, 40 (1). pp. 3-8. ISSN 0006-2960. doi:10.1021/bi0022339.

[img] PDF (Excitation and emission spectra of 2-AP containing duplex complexed with hairpin polyamide, fluorescence of pre-equilibrated complex of 2.5 μM hairpin + 2.5 μM matched duplex mixed with 1× TKMC, and stopped-flow traces for dissociation of indicated ...) - Supplemental Material
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Polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) subunits can bind in the minor groove of DNA at predetermined sequences with subnanomolar affinity and high specificity. Covalent linkage of polymer subunits using a gamma-aminobutyric acid linker has been shown to increase both the affinity and specificity of polyamides. Using a fluorescence detected stopped-flow assay, we have studied the differences in association and dissociation kinetics of a series of polyamides representing unlinked, hairpin and cyclic analogues of the four ring polyamide ImPyPyPy-beta-Dp. Whereas the large differences seen in the equilibrium association constants between the unlinked and covalently linked polyamides are primarily due to higher association rate constants, discrimination between matched and mismatched sites by each polyamide can be ascribed in large part to differences in their dissociation rate constants. The consequences of this kinetic behavior for future design are discussed.

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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2001 American Chemical Society. Received September 22, 2000. Publication Date (Web): December 7, 2000. We would like to thank Professors Axel Brunger, Alanna Schepartz, and Andrew Hamilton for allowing use of their instruments, NIH for funding this work (GM 21966 and GM 27681), and GeneSoft Inc. for salary support to R.B. in the laboratory of D.M.C.
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Official Citation:Kinetic Consequences of Covalent Linkage of DNA Binding Polyamides Ramesh Baliga, Eldon E. Baird, David M. Herman, Christian Melander, Peter B. Dervan, and Donald M. Crothers Biochemistry 2001 40 (1), 3-8 DOI: 10.1021/bi0022339
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66843
Deposited By: Victoria Brennan
Deposited On:18 May 2016 20:15
Last Modified:11 Nov 2021 00:22

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