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https://hdl.handle.net/2440/47991
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Type: | Journal article |
Title: | Molecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: Synthesis and evaluation of their binding properties |
Author: | Van Vliet, L. Ellis, T. Foley, P. Liu, L. Pfeffer, F. Russell, R. Warrener, R. Hollfelder, F. Waring, M. |
Citation: | Journal of Medicinal Chemistry, 2007; 50(10):2326-2340 |
Publisher: | Amer Chemical Soc |
Issue Date: | 2007 |
ISSN: | 0022-2623 1520-4804 |
Statement of Responsibility: | Liisa D. Van Vliet, Tom Ellis, Patrick J. Foley, Ligong Liu, Frederick M. Pfeffer, Richard A. Russell, Ronald N. Warrener, Florian Hollfelder, and Michael J. Waring |
Abstract: | We have exploited the concept of multivalency in the context of DNA recognition, using novel chemistry to synthesize a new type of bis-intercalator with unusual sequence-selectivity. Bis-intercalation has been observed previously, but design principles for de novo construction of such molecules are not known. Our compounds feature two aromatic moieties projecting from a rigid, polynorbornane-based scaffold. The length and character of the backbone as well as the identity of the intercalators were varied, resulting in mono- or divalent recognition of the double helix with varying affinity. Our lead compound proved to be a moderately sequence-selective bis-intercalator with an unwinding angle of 27 degrees and a binding constant of about 8 microM. 9-aminoacridine rings were preferred over acridine carboxamides or naphthalimides, and a rigid [3]-polynorbornane scaffold was superior to a [5]-polynorbornane. The flexibility of the linker connecting the rings to the scaffold, although less influential, could affect the strength and character of the DNA binding. |
Keywords: | Amides Norbornanes Acridines Aminoacridines Deoxyribonucleases DNA Intercalating Agents Dialysis Electrophoresis, Gel, Two-Dimensional Structure-Activity Relationship Naphthalimides |
Description: | Copyright © 2007 American Chemical Society |
DOI: | 10.1021/jm0613020 |
Published version: | http://pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/2007/50/i10/abs/jm0613020.html |
Appears in Collections: | Adelaide Graduate Centre publications Aurora harvest |
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