Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)
| Autor: | Prabal Giri, Gopinatha Suresh Kumar, Maidul Hossain |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Circular dichroism Stereochemistry Berberine Alkaloids In Vitro Techniques Biochemistry chemistry.chemical_compound Structural Biology Molecule Humans Binding site Molecular Biology Binding selectivity Binding Sites Molecular Structure Viscosity Circular Dichroism Osmolar Concentration Palmatine General Medicine DNA Kinetics Spectrometry Fluorescence chemistry Spectrophotometry Nucleic acid Nucleic Acid Conformation Thermodynamics Poly A Lead compound Dialysis |
| Zdroj: | International journal of biological macromolecules. 39(4-5) |
| ISSN: | 0141-8130 |
| Popis: | The interaction of the protoberberine alkaloid palmatine with single and double stranded structures of poly(A) was studied by various biophysical techniques. Comparative binding studies were also performed with double stranded DNA, t-RNA, poly(C).poly(G), poly(U) and poly(C). The results of competition dialysis, fluorescence, and absorption spectral studies converge to reveal the molecular aspects of the strong and specific binding of palmatine to single stranded poly(A). The binding affinity of palmatine to natural DNA, t-RNA and double stranded poly(A) was weaker while no binding was apparent with single stranded poly(U), poly(C) and double stranded poly(C).poly(G). The strong affinity of the alkaloid to single stranded poly(A) in comparison to the double stranded structure was also revealed from circular dichroic and viscometric studies. The effect of [Na+] ion concentration on the binding process revealed the significant role of electrostatic forces in the complexation. The presence of bound alkaloid also remarkably affected denaturation-renaturation of stacked helical poly(A). The energetics of the strong binding to poly(A) was studied from thermodynamic estimation from van Hoff' analysis of the temperature dependent binding constants and ultra sensitive isothermal titration calorimertry, both suggesting the binding to be exothermic and enthalpy driven. This study provides detailed insight into the binding specificity of the natural alkaloid to single stranded poly(A) over several other single and double stranded nucleic acid structures suggesting its potential as a lead compound for RNA based drug targeting. |
| Databáze: | OpenAIRE |
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