Design, Synthesis, and DNA Binding Properties of Photoisomerizable Azobenzene−Distamycin Conjugates: An Experimental and Computational Study

Ghosh, Sumana and Usharani, Dandamudi and Paul, Ananya and De, Susmita and Jemmis, Eluvathingal D and Bhattacharya, Santanu (2008) Design, Synthesis, and DNA Binding Properties of Photoisomerizable Azobenzene−Distamycin Conjugates: An Experimental and Computational Study. In: Bioconjugate Chemistry, 19 (12). pp. 2332-2345.

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Abstract

Here, we present the synthesis, photochemical, and DNA binding properties of three photoisomerizable azobenzene−distamycin conjugates in which two distamycin units were linked via electron-rich alkoxy or electron-withdrawing carboxamido moieties with the azobenzene core. Like parent distamycin A, these molecules also demonstrated AT-specific DNA binding. Duplex DNA binding abilities of these conjugates were found to depend upon the nature and length of the spacer, the location of protonatable residues, and the isomeric state of the conjugate. The changes in the duplex DNA binding efficiency of the individual conjugates in the dark and with their respective photoirradiated forms were examined by circular dichroism, thermal denaturation of DNA, and Hoechst displacement assay with poly[d(A-T).d(T-A)] DNA in 150 mM NaCl buffer. Computational structural analyses of the uncomplexed ligands using ab initio HF and MP2 theory and molecular docking studies involving the conjugates with duplex d[(GC(AT)10CG)]2 DNA were performed to rationalize the nature of binding of these conjugates.

Item Type:	Journal Article
Publication:	Bioconjugate Chemistry
Publisher:	American Chemical Society
Additional Information:	Copyright of this article belongs to American Chemical Society.
Department/Centre:	Division of Chemical Sciences > Organic Chemistry Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	11 Mar 2010 07:03
Last Modified:	19 Sep 2010 05:56
URI:	http://eprints.iisc.ac.in/id/eprint/26103

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