Quinacrine and 9-Amino Acridine Inhibit B-Z and B-HL Form DNA Conformational Transitions

Das, Suman and Kundu, Suprabhat and Kumar, G Suresh (2011) Quinacrine and 9-Amino Acridine Inhibit B-Z and B-HL Form DNA Conformational Transitions. DNA and Cell Biology, 30 (7). pp. 525-535.

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    Abstract

    The interaction of quinacrine and 9-amino acridine with right-handed B-form, left-handed Z-form, and lefthanded protonated (HL)-form structures of polydG-me5dC was investigated by circular dichroism and absorption spectral analysis. Both the compounds bind strongly to the B-form structure and convert the Z-form and HL-form back to the bound right-handed form. Circular dichroic data revealed that the conformation at the binding site is right-handed even though adjacent regions of the polynucleotide may have left-handed conformation. The rate and extent of B-form–to–Z-form transition were decreased in the presence of these compounds. Scatchard analysis revealed that both quinacrine and 9-amino acridine bind strongly to the polynucleotide in the B-form in a noncooperative manner, in sharp contrast to the highly cooperative binding to the Z-form and HL- form. Results indicated that the cooperative binding of these drugs with the Z-form and the HL-forms was associated with a sequential conversion of the polynucleotide from a left-handed to a bound right-handed conformation. Experimental data enabled the calculation of the number of base pairs of Z-form (7–8 with quinacrine and 9-amino acridine) and HL-form (4 and 25, respectively, with quinacrine and 9-amino acridine) that adopt a right-handed conformation for each bound ligand. As these compounds are known to bind preferentially to alternating guanine–cytosine sequences, which are capable of easily undergoing the B-to-Z or B-to- HL transition, these effects may be important in understanding their biological activities.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/95
    Subjects: Chemistry
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 28 Sep 2011 14:08
    Last Modified: 11 Jan 2013 11:37
    Official URL: http://dx.doi.org/10.1089/dna.2010.1206
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