Molecular Recognition of DNA by Rigid [n]-Polynorbornane-Derived Bifunctional Intercalators: Synthesis and Evaluation of Their Binding Properties
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- 作者：Liisa D. Van Vliet ; Tom Ellis ; Patrick J. Foley ; Ligong Liu ; Frederick M. Pfeffer ; Richard A. Russell ; Ronald N. Warrener ; Florian Hollfelder ; Michael J. Waring
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：May 17, 2007
- 年：2007
- 卷：50
- 期：10
- 页码：2326 - 2340
- 全文大小：566K
- 年卷期：v.50,no.10(May 17, 2007)
- ISSN：1520-4804
文摘
We have exploited the concept of multivalency in the context of DNA recognition, using novel chemistryto synthesize a new type of bis-intercalator with unusual sequence-selectivity. Bis-intercalation has beenobserved previously, but design principles for de novo construction of such molecules are not known. Ourcompounds feature two aromatic moieties projecting from a rigid, polynorbornane-based scaffold. The lengthand character of the backbone as well as the identity of the intercalators were varied, resulting in mono- ordivalent recognition of the double helix with varying affinity. Our lead compound proved to be a moderatelysequence-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 connectingthe rings to the scaffold, although less influential, could affect the strength and character of the DNA binding.
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 connectingthe rings to the scaffold, although less influential, could affect the strength and character of the DNA binding.