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Biophysical studies of mutated K562 DNA (erythroleukemic cells) binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing binding behavior

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Biophysical studies of mutated K562 DNA (erythroleukemic cells) binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing binding behavior
 
Creator Ghosh, Debjani
Saha, Chabita
Hossain, Maidul
Dey, Subrata Kumar
Kumar, G Suresh
 
Subject Chemistry
 
Description K562 cells are erythroleukemic cells derived from a chronic myeloid leukemia patient in blast crisis. Comparison of the genome from K562 cells and normal human genome has been very useful strategy, in uncovering eight genes, implicated in acute myeloid leukemia (AML). These genes carry mutations in K562 genome and the role of these mutations in the progression and treatment of AML is still not known. Consequences of these mutations on drug DNA binding are also not known exactly. In the present study, mutation induced structural changes in K562 genome, compared to normal genome, are identified by Fourier transform infra red (FTIR) and circular dichroism (CD) spectroscopy. These structural changes in native K562 DNA favor stronger binding with binding constants 2.0�108 and 1.9�109M�1 with antileukemic drugs adriamycin and daunomycin (DNM), respectively, compared to normal DNA. On binding, these drugs disrupt the native B form structure of normal DNA to a greater extent, compared to A-like structure of K562 DNA. Fluorescence and absorption studies reveal higher intercalation as well as mixed groove binding of these drugs with K562 DNA compared to normal DNA. Among the drugs, DNM has higher affinity for K562 DNA
 
Date 2013
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1931/1/JOURNAL_OF_BIOMOLECULAR_STRUCTURE_%26_DYNAMICS___31(_3_)331%2D341;2013[62].pdf
Ghosh, Debjani and Saha, Chabita and Hossain, Maidul and Dey, Subrata Kumar and Kumar, G Suresh (2013) Biophysical studies of mutated K562 DNA (erythroleukemic cells) binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing binding behavior. Journal of Biomolecular Structure and Dynamics, 31 (3). pp. 331-341.
 
Relation http://dx.doi.org/10.1080/07391102.2012.698190
http://www.eprints.iicb.res.in/1931/