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Distamycin Analogues without Leading Amide at Their N-Termini-Comparative Binding Properties to AT- and GC-Rich DNA Sequences

Thomas, Mini and Varshney, Umesh and Bhattacharya, Santanu (2002) Distamycin Analogues without Leading Amide at Their N-Termini-Comparative Binding Properties to AT- and GC-Rich DNA Sequences. In: European Journal of Organic Chemistry, 2002 (21). pp. 3604-3615.


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An efficient, simple and general route towards the solution-phase synthesis of four distamycin analogues containing 2-5 N-methylcarboxamide units without the leading amide unit at the N-terminus is described. The binding abilities of these molecules to calf thymus DNA, poly d(AT), poly dA.poly dT and poly d(GC) were evaluated by duplex DNA melting temperature (Tm) analysis, fluorescence probe displacement assay, footprinting studies and induced circular dichroism (ICD) measurements. A minimum of three N-methylpyrrolecarboxamide units was found to be necessary for the onset of DNA binding. The other three analogues exhibited AT-specific footprints on DNA at a salt concentration of 40 mM NaCl. Interestingly, intense ICD spectra were obtained not only with AT-rich DNA tracts, but also with poly d(GC). Though these ICD signals were sensitive to changes in salt concentration of the solution, residual ICD was present even at [NaCl] values as high as 4.8 M, at which poly d(GC) is likely to exist in the Z conformation. This implies that nonelectrostatic interactions are involved in the binding process involving poly d(GC) and also that binding is preserved even with the Z form of DNA. These results have significance on account of the growing interest in polyamide-based minor groove binders as artificial gene regulators and also in view of the increasing evidence for the biological significance of the Z morph of DNA.

Item Type: Journal Article
Publication: European Journal of Organic Chemistry
Publisher: WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information: The DOI is currently only displayed. The copyright of this article belongs to WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keywords: AT and GC recognition;Distamycin analogues;DNA recognition;Drug research;Synthesis
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Division of Chemical Sciences > Organic Chemistry
Date Deposited: 21 Jul 2004
Last Modified: 19 Sep 2010 04:14
URI: http://eprints.iisc.ac.in/id/eprint/1080

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