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Assessment of amsacrine binding with DNA using UV–visible, circular dichroism and Raman spectroscopic techniques

Paper ID Volume ID Publish Year Pages File Format Full-Text
30739 44500 2012 6 PDF Available
Title
Assessment of amsacrine binding with DNA using UV–visible, circular dichroism and Raman spectroscopic techniques
Abstract

Proper understanding of the mechanism of binding of drugs to their targets in cell is a fundamental requirement to develop new drug therapy regimen. Amsacrine is a rationally designed anticancer drug, used to treat leukemia and lymphoma. Binding with cellular DNA is a crucial step in its mechanism of cytotoxicity. Despite numerous studies, DNA binding properties of amsacrine are poorly understood. Its reversible binding with DNA does not permit X-ray crystallography or NMR spectroscopic evaluation of amsacrine–DNA complexes. In the present work, interaction of amsacrine with calf thymus DNA is investigated at physiological conditions. UV–visible, FT-Raman and circular dichroism spectroscopic techniques were employed to determine the binding mode, binding constant, sequence specificity and conformational effects of amsacrine binding to native calf thymus DNA. Our results illustrate that amsacrine interacts with DNA by and large through intercalation between base pairs. Binding constant of the amsacrine–DNA complex was found to be K = 1.2 ± 0.1 × 104 M−1 which is indicative of moderate type of binding of amsacrine to DNA. Raman spectroscopic results suggest that amsacrine has a binding preference of intercalation between AT base pairs of DNA. Minor groove binding is also observed in amsacrine–DNA complexes. These results are in good agreement with in silico investigation of amsacrine binding to DNA and thus provide detailed insight into DNA binding properties of amsacrine, which could ultimately, renders its cytotoxic efficacy.

► Amsacrine binds with DNA through intercalation and minor groove interactions. ► Binding constant shows that amsacrine is a moderate binder. ► Amsacrine preferably intercalates between AT base pairs. ► Amsacrine interaction perturbs the native B conformation of DNA.

Keywords
Amsacrine; DNA; Interaction mechanism; FT-Raman spectroscopy; CD spectroscopy; DNA–amsacrine model
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Assessment of amsacrine binding with DNA using UV–visible, circular dichroism and Raman spectroscopic techniques
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 114, 3 September 2012, Pages 38–43
Authors
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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