Date Published: July 24, 2013
Publisher: Public Library of Science
Author(s): Ayesha Kabir, Gopinatha Suresh Kumar, Heidar-Ali Tajmir-Riahi.
The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results.
Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines.
From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.
Polyamines (Fig. 1) are cardinal indispensible molecules which sustain the structure, conformation, and function of nucleic acids and proteins thereby affecting cell growth and orchestrate cellular regulatory pathways and functions like gene regulation, DNA packaging, proliferation etc –. Numerous studies have shown that polyamines accumulate in cancer cells and a higher concentration of polyamines is usually correlated to cancerous growth. Studies have also demonstrated that a reduction of polyamine concentration usually has cytotoxic effects on cells through inhibition of growth or promotion of apoptosis in the cell. The effectiveness of polyamine analogs as antiproliferative agents against many tumor cell lines provides evidence for nucleic acid interaction –. Polyamines interaction with nucleic acids have also been shown to affect the stability of double and triple stranded DNA, protect DNA from oxidative stress, damaging agents, ionizing radiation, and endonuclease digestion etc –.