Molecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: synthesis and evaluation of their binding properties

Van Vliet, Liisa, Ellis, Tom, Foley, Patrick, Liu, Ligong, Pfeffer, Frederick, Russell, Richard, Warrener, Ronald, Hollfelder, Florian and Waring, Michael 2007, Molecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: synthesis and evaluation of their binding properties, Journal of medicinal chemistry, vol. 50, no. 10, pp. 2326-2340.


Title Molecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: synthesis and evaluation of their binding properties
Formatted title Molecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: synthesis and evaluation of their binding properties
Author(s) Van Vliet, Liisa
Ellis, Tom
Foley, Patrick
Liu, Ligong
Pfeffer, Frederick
Russell, Richard
Warrener, Ronald
Hollfelder, Florian
Waring, Michael
Journal name Journal of medicinal chemistry
Volume number 50
Issue number 10
Start page 2326
End page 2340
Publisher American Chemical Society
Place of publication Wash. D.C.
Publication date 2007
ISSN 0022-2623
1520-4804
Summary 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 and a binding constant of about 8 M. 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.
Language eng
Field of Research 030405 Molecular Medicine
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2007, American Chemical Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30007425

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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