Discriminating Intercalative Effects of Threading Intercalator Nogalamycin, from Classical Intercalator Daunomycin, Using Single Molecule Atomic Force Spectroscopy

• Published in: PloS one Vol. 11; no. 5; p. e0154666
• Main Authors: Banerjee, T, Banerjee, S, Sett, S, Ghosh, S, Rakshit, T, Mukhopadhyay, R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.05.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Antibiotics; Atomic beam spectroscopy; Atomic force microscopy; Biochemistry; Biology; Biology and life sciences; Chemistry; Contours; Daunomycin; Daunorubicin; Daunorubicin - chemistry; Deoxyribonucleic acid; DNA; DNA - chemistry; Dosage and administration; Experiments; Gene expression; Incubation; Intercalating agents; Intercalating Agents - chemistry; Kinetics; Medicine and Health Sciences; Microscopy; Microscopy, Atomic Force; Molecular Structure; Nogalamycin; Nogalamycin - chemistry; Physical Sciences; Research and Analysis Methods; Science; Shape; Spectroscopy; Spectrum Analysis; Substance abuse treatment; United States > US; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154666

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.