Dimeric and trimeric derivatives of the azinomycin B chromophore show enhanced DNA binding

作者：Balazy Milena; Fausto Alejandra; Voskanian Christina; Chavez Bianca; Panesar Harmanpreet; Minehan Thomas G^*

来源：Organic and Biomolecular Chemistry, 2017, 15(21): 4522-4526.

DOI：10.1039/c7ob00944e

To explore the utility of the azinomycin B chromophore as a platform for the development of major-groove binding small molecules, we have prepared a series of 3-methoxy-5-methylnaphthalene derivatives containing diamine, triamine, and carbohydrate linker moieties. All bis- and tris-azinomycin derivatives are intercalators that display submicromolar binding affinities for calfthymus DNA, as revealed by viscometry measurements and fluorescent intercalator displacement (FID) assays, respectively. Although the tightest binding ligand 1d (K-a = 2.42 x 10(7) M-1) has similar affinities for sequence diverse polynucleotides, competition binding studies with methylated phage DNA and known major and minor groove binding small molecules suggest that the tether moiety linking the naphthalene chromophores may occupy the major groove of DNA.

• 出版日期2017-6-7