fulltext.study @t Gmail

Elucidation of the DNA binding specificity of the natural plant alkaloid chelerythrine: A biophysical approach

Paper ID Volume ID Publish Year Pages File Format Full-Text
30307 44468 2014 13 PDF Available
Title
Elucidation of the DNA binding specificity of the natural plant alkaloid chelerythrine: A biophysical approach
Abstract

•Chelerythrine exhibits high specificity to GC base pairs over AT base pairs.•The binding affinity to the polynucleotides is of the order 106 M−1.•Intercalation of the alkaloid results in energy transfer from base to alkaloid.•The binding is favoured by negative enthalpy and positive entropy changes in GC sequences.•The binding was driven by multiple weak noncovalent forces.

Interaction of the anticancer plant alkaloid chelerythrine with four sequence specific synthetic polynucleotides was studied by spectroscopy and calorimetry experiments. The binding resulted in strong hypochromic and bathochromic effects in the absorption spectrum of the alkaloid, enhancement in the fluorescence with the AT polynucleotides and the homo-GC polynucleotide and quenching with the hetero-GC polynucleotide. Cooperative binding was observed with all the polynucleotides. Fluorescence polarization anisotropy, iodide quenching and viscosity results confirmed intercalative binding of the alkaloid. The binding resulted in the thermal stabilization of the polynucleotides and moderate perturbations in the B-conformation of the DNA. The high binding affinity values (∼106 M−1) evaluated from the spectroscopic data was in excellent agreement with those obtained from calorimetry. The binding was exothermic and favoured by negative standard molar enthalpy and positive standard molar entropic contributions in all cases other than homo-AT polynucleotide, where it was endothermic and entropy driven. Salt-dependent calorimetry data revealed that the binding reaction was driven mostly by non-polyelectrolytic forces. The magnitude of the negative heat capacity values confirmed the role of significant hydrophobic effects in the interaction profile of the alkaloid with the polynucleotides. The results revealed the specificity of chelerythrine to follow homo-GC > hetero-GC > hetero-AT = homo-AT polynucleotide.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
Benzophenanthridine alkaloid; Polynucleotides; Specificity; Thermodynamics
First Page Preview
Elucidation of the DNA binding specificity of the natural plant alkaloid chelerythrine: A biophysical approach
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 138, 5 September 2014, Pages 282–294
Authors
, ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us