Unusual DNA binding exhibited by synthetic distamycin analogues lacking the N-terminal amide unit under high salt conditions

Thomas, Mini and Rao, Arasada Rajeswara and Varshney, Umesh and Bhattacharya, Santanu (2001) Unusual DNA binding exhibited by synthetic distamycin analogues lacking the N-terminal amide unit under high salt conditions. In: Journal Of Biomolecular Structure & Dynamics, 18 (6). pp. 858-871.

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Abstract

The binding of three analogues of the minor-groove binding antiviral antibiotic distamycin (Dst) with double-stranded (ds)-DNA were monitored using ds-DNA melting temperature (T,) measurements, ethidium bromide (EtBr) displacement assay, footprinting analysis and induced circular dichroism (ICD). These compounds contained 3-5 N-methyl-pyrrole-carboxamide units and lacked the N-terminal formamide unit present in Dst. These experiments suggested that the present analogues did not compromise their AT-specificity despite the deletion of the N-terminal formamide unit. The binding affinities, however, were significantly affected. Interestingly, the analogue with three N-methyl-pyrrole-carboxamide units exhibited an initial decrease in ICD at > 40 mM salt concentrations. This was followed by a pronounced recovery of ICD at > 1.6 M salt concentrations, a phenomenon hitherto not observed with any other DNA binding molecules. The pentapyrrole analogue exhibited the highest binding affinity with CT-DNA under normal (40 mM) salt conditions. However, it suffered maximum relative dissociation under high salt conditions and did not exhibit any recovery in ICD at higher NaCl concentrations. The analogues possessing four and five pyrrole rings exhibited intense ICD signals with poly d(GC) in the ligand absorption region in the presence of 40 mM NaCl, unlike the one with three pyrrole rings. These ICD signals were however, highly susceptible to changes in ionic strength. Thus subtle modifications in the ligand molecular structure can have dramatic effect on their DNA binding properties.

Item Type:	Journal Article
Publication:	Journal Of Biomolecular Structure & Dynamics
Publisher:	Adenine Press
Additional Information:	Copyright of this article belongs to Adenine Press.
Keywords:	Minor-groove recognition; nucleic-acid sequences; molecular recognition; deoxyribonucleic-acid; linked lexitropsins; circular-dichroism; chain length; b-form; netropsin; complex
Department/Centre:	Division of Chemical Sciences > Organic Chemistry Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	10 Feb 2010 05:49
Last Modified:	19 Sep 2010 04:59
URI:	http://eprints.iisc.ac.in/id/eprint/17902

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