DNA-Binding Cytotoxic Alkaloids: Comparative Study of the Energetics of Binding of Berberine, Palmatine, and Coralyne
EPrints@IICB
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Title |
DNA-Binding Cytotoxic Alkaloids: Comparative Study of the Energetics of Binding of Berberine, Palmatine, and Coralyne
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Creator |
Bhadra, Kakali
Maiti, Motilal Kumar, G Suresh |
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Subject |
Chemistry
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Description |
Deoxyribonucleic acid is the site of storage and retrieval of genetic information through interaction with proteins and other small molecules. In the present study, the interaction of two natural cytotoxic protoberberine plant alkaloids, berberine and palmatine, and a synthetic derivative, coralyne, withmammalian herring testis DNA was investigated using a combination of isothermal titration calorimetry, differential scanning calorimetry, and optical melting experiments to characterize the energetics of their binding. The binding constants of these alkaloids to DNA under identical conditions were evaluated from the UV melting data, and the enthalpy of binding was elucidated from isothermal titration studies. The binding constants of berberine, palmatine, and coralyne to DNA were found to be 1.15�104, 2.84�104, and 3.5�106M�1 at 208C in buffer of 20mM[Na+]. Parsing of the free energy change of the interaction observed into polyelectrolytic and nonpolyelectrolytic components suggested that although these alkaloids are charged, the major contributor of about 75% of the binding free energy arises from the nonpolyelectrolytic forces. The binding in case of palmatine and coralyne was predominantly enthalpy driven with favoring smaller entropy terms, while that of berberine was favored by both negative enthalpy and positive entropy changes. Temperature dependence of the binding enthalpies determined from ITC studies in the range 20– 408C was used to calculate the binding-induced change in heat capacity (DCo p) values as �117, �135, and �157 cal=mol K, respectively, for berberine, palmatine, and coralyne. Taken together, the results suggest that the DNA binding of the planar synthetic coralyne is stronger and thermodynamically more favored compared to the buckled natural berberine and palmatine. |
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Date |
2008
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/148/1/DNA_AND_CELL_BIOLOGY%2C27(12)%2C675%2D685%2C2008[10].pdf
Bhadra, Kakali and Maiti, Motilal and Kumar, G Suresh (2008) DNA-Binding Cytotoxic Alkaloids: Comparative Study of the Energetics of Binding of Berberine, Palmatine, and Coralyne. DNA and Cell Biology, 27 (12). pp. 675-685. |
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Relation |
http://dx.doi.org/10.1089=dna.2008.0779
http://www.eprints.iicb.res.in/148/ |
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