Effect of the bases flanking an abasic site on the recognition of nucleobase by amiloride |
| |
Authors: | Arivazhagan Rajendran Chunxia Zhao Burki Rajendar Viruthachalam Thiagarajan Yusuke Sato Seiichi Nishizawa Norio Teramae |
| |
Institution: | 1. Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan;2. CREST, Japan Science and Technology Agency (JST), Aoba-ku, Sendai 980-8578, Japan |
| |
Abstract: | BackgroundWe explain here the various non-covalent interactions which are responsible for the different binding modes of a small ligand with DNA.MethodsThe combination of experimental and theoretical methods was used.ResultsThe interaction of amiloride with thymine was found to depend on the bases flanking the AP site and different binding modes were observed for different flanking bases. Molecular modeling, absorption studies and binding constant measurements support for the different binding patterns. The flanking base dependent recognition of AP site phosphates was investigated by 31P NMR experiments. The thermodynamics of the ligand–nucleotide interaction was demonstrated by isothermal titration calorimetry. The emission behavior of amiloride was found to depend on the bases flanking the AP site. Amiloride photophysics in the context of AP-site containing DNA is investigated by time-dependent density functional theory.ConclusionsFlanking bases affect the ground and excited electronic states of amiloride when binding to AP site, which causes flanking base-dependent fluorescence signaling.General significanceThe various noncovalent interactions have been well characterized for the determination of nucleic acid structure and dynamics, and protein–DNA interactions. However, these are not clear for the DNA–small molecule interactions and we believe that our studies will bring a new insight into such phenomena. |
| |
Keywords: | SNP single nucleotide polymorphism AP abasic DCPC 3 5-diamino-6-chloro-2-pyrazinecarbonitrile TDDFT time dependent density functional theory Spacer C3 Spacer phosphoramidite C3 ITC isothermal titration calorimetry CV cyclic voltammetry MM molecular mechanics HOMO highest occupied molecular orbital LUMO lowest unoccupied molecular orbital CT charge transfer |
本文献已被 ScienceDirect 等数据库收录! |
|