Designed Compounds for Recognition of 10 Base Pairs of DNA with Two AT Binding Sites

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• 作者：Yang Liu ; Yun Chai ; Arvind Kumar ; Richard R. Tidwell ; David W. Boykin ; W. David Wilson
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：March 21, 2012
• 年：2012
• 卷：134
• 期：11
• 页码：5290-5299
• 全文大小：581K
• 年卷期：v.134,no.11(March 21, 2012)
• ISSN：1520-5126

文摘

Short AT base pair sequences that are separated by a small number of GCs are common in eukaryotic parasite genomes. Cell-permeable compounds that bind effectively and selectively to such sequences present an attractive therapeutic approach. Compounds with linked, one or two amidine-benzimidazole-phenyl (ABP) motifs were designed, synthesized, and evaluated for binding to adjacent AT sites by biosensor-surface plasmon resonance (SPR). A surprising feature of the linked ABP motifs is that a set of six similar compounds has three different minor groove binding modes with the target sequences. Compounds with one ABP bind independently to two separated AT sites. Unexpectedly, compounds with two ABP motifs can bind strongly either as monomers or as cooperative dimers to the full site. The results are supported by mass spectrometry and circular dichroism, and models to explain the different binding modes are presented.