Discriminating Intercalative Effects of Threading Intercalator Nogalamycin, from Classical Intercalator Daunomycin, Using Single Molecule Atomic Force Spectroscopy
DNA threading intercalators are a unique class of intercalating agents, albeit little biophysical information is available on their intercalative actions. Herein, the intercalative effects of nogalamycin, which is a naturally-occurring DNA threading intercalator, have been investigated by high-resol...
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Published in | PloS one Vol. 11; no. 5; p. e0154666 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
16.05.2016
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | DNA threading intercalators are a unique class of intercalating agents, albeit little biophysical information is available on their intercalative actions. Herein, the intercalative effects of nogalamycin, which is a naturally-occurring DNA threading intercalator, have been investigated by high-resolution atomic force microscopy (AFM) and spectroscopy (AFS). The results have been compared with those of the well-known chemotherapeutic drug daunomycin, which is a non-threading classical intercalator bearing structural similarity to nogalamycin. A comparative AFM assessment revealed a greater increase in DNA contour length over the entire incubation period of 48 h for nogalamycin treatment, whereas the contour length increase manifested faster in case of daunomycin. The elastic response of single DNA molecules to an externally applied force was investigated by the single molecule AFS approach. Characteristic mechanical fingerprints in the overstretching behaviour clearly distinguished the nogalamycin/daunomycin-treated dsDNA from untreated dsDNA-the former appearing less elastic than the latter, and the nogalamycin-treated DNA distinguished from the daunomycin-treated DNA-the classically intercalated dsDNA appearing the least elastic. A single molecule AFS-based discrimination of threading intercalation from the classical type is being reported for the first time. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: TB SB RM. Performed the experiments: TB SB SS SG. Analyzed the data: SB SS TR RM. Contributed reagents/materials/analysis tools: RM. Wrote the paper: SB SS RM. Current address: School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44106, United States of America Current address: Department of Chemistry, MVJCE, Bangalore, 560067, India Current address: College of Pharmacy, University of Nebraska Medical Center (UNMC), Omaha, Nebraska, 68198–6025, United States of America These authors are first authors on this work. Current address: Department of Chemistry, New Alipore College, Kolkata, 700053, India |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0154666 |