The Journal of Biological Physics and Chemistry

Emergence of pregenetic coding in a prebiotic ecology

J.R. Monaselidze, S.V. Barbakadze, M.T. Kiladze, M.Z. Gorgoshidze, D.G. Khachidze and G.V. Majagaladze

E. Andronikashvili Institute of Physics, 6 Tamarashvili St, 0177 Tbilisi, Georgia


The influence of a new anticancerogenic drug, TOEPyP(4) (meso-tetra-(4-N-oxyethylpyridyl) porphyrin) (an analogue of TMPy4 (tetra(N-methyl-4-pyridyl)-porphyrin chloride), a G-quadruplex intercalating porphyrin), a telomerase inhibitor, on the thermodynamic stability of DNA in vitro has been studied. TOEPyP(4) is a stronger stabilizing DNA agent than TMPyP4, causing an increase of thermostability by 20 °C. Electrostatic interactions between the positively charged nitrogen atoms of the TOEPyP(4) pyridyl rings and the negatively charged phosphate groups of the DNA result in the pyridyl rings intercalating between the G and C pairs of the duplex to form the G-quadruplex (outer groove binding). These interactions do not disturb the DNA double helix; the melting enthalpy (ΔH_m) remains unchanged; the melting entropy (ΔS_m) decreases because of the sharp increase of helix state entropy due to disorganization of the ordered water structure in the exclusive binding sites of Cu(II)TOEPyP(4) with DNA. This result is extremely important for pharmacology as it implies that many cytostatic drugs used at present, even in μg quantities, damage DNA to a significant degree.

Keywords: DNA-TOEPyP(4) complex melting, microcalorimeter, porphyrin