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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
Statement of
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
RMID: 0020070758
DOI: 10.1021/jm0613020
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Appears in Collections:Adelaide Graduate Centre publications

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