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Interaction of Isoquinoline Alkaloid Palmatine with Deoxyribonucleic Acids: Binding Heterogeneity, and Conformational and Thermodynamic Aspects
Author(s) -
Bhadra Kakali,
Maiti Motilal,
Kumar Gopinatha Suresh
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890054
Subject(s) - chemistry , isothermal titration calorimetry , palmatine , stereochemistry , circular dichroism , dna , cooperativity , conformational entropy , base pair , cooperative binding , dabco , binding site , alkaloid , molecule , crystallography , biochemistry , organic chemistry , catalysis
The binding heterogeneity, conformational aspects, and energetics of the interaction of the cytotoxic plant alkaloid palmatine have been studied with various natural and synthetic DNAs. The alkaloid binds to calf thymus and Escherichia coli DNA that have mixed AT and GC sequences in almost equal proportions with positive cooperativity, while, with Clostridium perfringens and Micrococcus lysodeikticus DNA with predominantly high AT and GC sequences, respectively, noncooperative binding was observed. On further investigation with synthetic DNAs, the binding was observed to be cooperative with polymers like poly(dA)⋅poly(dT) and poly(dG)⋅poly(dC) having poly(purine)⋅poly(pyrimidine) sequences, while with polymers poly(dA‐dT)⋅poly(dA‐dT), poly(dA‐dC)⋅poly(dG‐dT) and poly(dG‐dC)⋅poly(dG‐dC), which have alternating purine‐pyrimidine sequences, a non‐cooperative binding phenomenon was observed. This suggests the binding heterogeneity of palmatine to the two types of sequences of base pairs. Circular dichroism (CD) studies revealed that the binding induced conformational changes in all the DNAs, but more importantly, the bound alkaloid molecules acquired induced optical activity, and the extent was dependent on the AT content and showed AT base‐pair specificity. Energetics of the interaction of the alkaloid studied by highly sensitive isothermal titration calorimetry revealed that the binding was in most cases exothermic and favored by both enthalpy and entropy changes, while, in the case of the homo and hetero AT polymers, the same was predominantly entropy‐driven. This study defines base‐pair‐dependent heterogeneity, conformational aspects, and energetics of palmatine binding to DNA.