Linker dependent intercalation of bisbenzimidazole-aminosugars in an RNA duplex; selectivity in RNA vs. DNA binding

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Ranjan, Nihar¹  Arya, Dev P.¹ 

[1] Clemson Univ, Dept Chem, Lab Bioorgan & Med Chem, Clemson, SC 29634 USA

关键词: Neomycin;    Hoechst 33258;    Intercalation;    RNA duplex;    Linear dichroism;   

DOI  :  10.1016/j.bmcl.2016.10.076

来源: Elsevier

【 摘 要 】

Neomycin and Hoechst 33258 are two well-known nucleic acid binders that interact with RNA and DNA duplexes with high affinities respectively. In this manuscript, we report that covalent attachment of bisbenzimidazole unit derived from Hoechst 33258 to neomycin leads to intercalative binding of the bisbenzimidazole unit (oriented at 64-74 with respected to the RNA helical axis) in a linker length dependent manner. The dual binding and intercalation of conjugates were supported by thermal denaturation, CD, LD and UV-Vis absorption experiments. These studies highlight the importance of linker length in dual recognition by conjugates, for effective RNA recognition, which can lead to novel ways of recognizing RNA structures. Additionally, the ligand library screens also identify DNA and RNA selective compounds, with compound 9, containing a long linker, showing a 20.3 degrees C change in RNA duplex T-m with only a 13.0 degrees C change in T-m for the corresponding DNA duplex. Significantly, the shorter linker in compound 3 shows almost the reverse trend, a 23.8 degrees C change in DNA T-m, with only a 9.1 degrees C change in T-m for the corresponding RNA duplex. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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