Insights on the interaction of phenothiazinium dyes methylene blue and new methylene blue with synthetic duplex RNAs through spectroscopy and modeling

June 29, 2020

Title

Insights on the interaction of phenothiazinium dyes methylene blue and new methylene blue with synthetic duplex RNAs through spectroscopy and modeling

Year

2020

Journal

Journal of Photochemistry and Photobiology B: Biology

Abstract

The ubiquitous influence of double stranded RNAs in biological events makes them imperative to gather data based on specific binding procedure of small molecules to various RNA conformations. Particular interest may be attributed to situations wherein small molecules target RNAs altering their structures and causing functional modifications. The main focus of this study is to delve into the interactive pattern of two small molecule phenothiazinium dyes, methylene blue and new methylene blue, with three duplex RNA polynucleotides-poly(A).poly(U), poly(C).poly(G) and poly(I).poly(C) by spectroscopic and molecular modeling techniques. Analysis of data as per Scatchard and Benesi-Hildebrand methodologies revealed highest affinity of these dyes to poly(A).poly(U) and least to poly(I).poly(C). In addition to fluorescence quenching, viscometric studies also substantiated that the dyes follow different modes of binding to different RNA polynucleotides. Distortion in the RNA structures with induced optical activity in the otherwise optically inactive dye molecules was evidenced from circular dichroism results. Dye-induced RNA structural modification occurred from extended conformation to compact particles visualized by atomic force microscopy. Molecular docking results revealed different binding patterns of the dye molecules within the RNA duplexes. The novelty of the present work lies towards a new contribution of the phenothiazinium dyes in dysfunctioning double stranded RNAs, advancing our knowledge to their potential use as RNA targeted small molecules.

Instrument

V-660, J-815

Keywords

Absorption, RNA binding, Circular dichroism, RNA structure, Ligand binding, Secondary structure, Biochemistry, Materials