Interaction of Isoquinoline Alkaloid Palmatine with Deoxyribonucleic Acids: Binding Heterogeneity, and Conformational and Thermodynamic Aspects
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Interaction of Isoquinoline Alkaloid Palmatine with Deoxyribonucleic Acids: Binding Heterogeneity, and Conformational and Thermodynamic Aspects
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| Creator |
Bhadra, Kakali
Maiti, Motilal Kumar, G Suresh |
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| Subject |
Chemistry
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| Description |
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 syntheticDNAs, 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(dGdC)
·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 entropydriven.
This study defines base-pair-dependent heterogeneity, conformational aspects, and energetics of
palmatine binding to DNA.
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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/276/1/CHEMISTRY_%26_BIODIVERSITY%2C_5_(4)%2C575%2D590%2C2008_[148].pdf
Bhadra, Kakali and Maiti, Motilal and Kumar, G Suresh (2008) Interaction of Isoquinoline Alkaloid Palmatine with Deoxyribonucleic Acids: Binding Heterogeneity, and Conformational and Thermodynamic Aspects. Chemistry and Biodiversity, 5 (4). pp. 575-590. |
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| Relation |
http://dx.doi.org/10.1002/cbdv.200890054
http://www.eprints.iicb.res.in/276/ |
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