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

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dc.contributor.authorVan Vliet, L.
dc.contributor.authorEllis, T.
dc.contributor.authorFoley, P.
dc.contributor.authorLiu, L.
dc.contributor.authorPfeffer, F.
dc.contributor.authorRussell, R.
dc.contributor.authorWarrener, R.
dc.contributor.authorHollfelder, F.
dc.contributor.authorWaring, M.
dc.date.issued2007
dc.descriptionCopyright © 2007 American Chemical Society
dc.description.abstractWe 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.
dc.description.statementofresponsibilityLiisa 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
dc.identifier.citationJournal of Medicinal Chemistry, 2007; 50(10):2326-2340
dc.identifier.doi10.1021/jm0613020
dc.identifier.issn0022-2623
dc.identifier.issn1520-4804
dc.identifier.urihttp://hdl.handle.net/2440/47991
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.source.urihttp://pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/2007/50/i10/abs/jm0613020.html
dc.subjectAmides
dc.subjectNorbornanes
dc.subjectAcridines
dc.subjectAminoacridines
dc.subjectDeoxyribonucleases
dc.subjectDNA
dc.subjectIntercalating Agents
dc.subjectDialysis
dc.subjectElectrophoresis, Gel, Two-Dimensional
dc.subjectStructure-Activity Relationship
dc.subjectNaphthalimides
dc.titleMolecular recognition of DNA by rigid [n]-polynorbornane-derived bifunctional intercalators: Synthesis and evaluation of their binding properties
dc.typeJournal article
pubs.publication-statusPublished

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