PubAg

Main content area

Targeting G-quadruplex DNA and B-DNA with a natural alkaloid: a comparative spectroscopic study

Author:
Mandal, Paulami, Bhattacharya, Maitree, Chowdhury, Joydeep
Source:
RSC advances 2016 v.6 no.111 pp. 109846-109856
ISSN:
2046-2069
Subject:
B-DNA, alkaloids, anisotropy, computer simulation, gene therapy, models, spectral analysis, spectroscopy, telomeres, toxicity
Abstract:
The present research compared the binding mechanisms of natural alkaloid harmine (HR) with two structurally different biologically important DNA species, human telomeric 22 G-quadruplex DNA (GQ-DNA) and B-DNA using various steady state and time-resolved spectroscopic techniques. Our study shows that for both DNA species HR has appreciable ground state interaction with comparable binding strengths. When HR binds, GQ-DNA which initially remained as mixed-hybrid structure converted to parallel types whereas the B-DNA structure perturbed through intercalation. HR displayed modest selectivity for the quadruplex over duplex B-DNA and binds in grooves and/or loops over external end stacking with quadruplex instead of intercalation with B-DNA. Switching of stabilization from moderate to strong occurred while HR binds with GQ-DNA and B-DNA respectively. The difference in the dynamics of HR in with both DNAs has been described well by the wobbling-in-cone model from the time-resolved anisotropy data. Our time-resolved results interpreted the dynamics of HR in both DNA environments suggesting favourable loop and/or groove binding of HR with GQ-DNA over partial end-stacking and intercalation mode of binding with B-DNA. Steady state anisotropy measurements and molecular docking further confirmed our conclusions regarding binding mechanisms. The present study could be highly useful in less toxic targeted gene therapy.
Agid:
6413344