SPECTROSCOPIC STUDY OF THE INTERACTION OF PAZELLIPTINE WITH NUCLEIC-ACIDS

The antitumor drug pazelliptine (PZE) binds to natural and synthetic D NA sequences at 100 mM NaCl, pH 7.0, as deduced from the absorption an d fluorescence data. Scatchard plots constructed from the results obta ined with poly(dG-dC)-poly(dG-dC) give binding constants of base pairs in the range (2-6) x 10(5) M-1. The modifications in the absorption a nd fluorescence spectra observed when PZE binds to various polynucleot ides, namely poly(dA-dT)-poly(dA-dT), poly(dA)-poly(dT), poly(dG-dC)-p oly(dG-dC) and calf thymus DNA, reveal a change in the protonation sta te of the drug upon binding, increasing the apparent pk(a) of its 9-N nitrogen atom. The PZE excited state properties serve as a sensitive p robe to distinguish between home and hetero A-T sites as well as betwe en AT and SC sites. Fluorescence studies reveal that energy transfer o ccurs from polynucleotide bases to the bound PZE chromophore, a result consistent with an intercalative mode of binding of the drug to DNA. The emission is enhanced when PZE is bound to A-T base pairs (similar to 30% increase of phi(F)) whereas it is quenched in the vicinity of G -C base pairs (similar to 90% decrease of phi(F)). Furthermore, the fl uorescence spectrum obtained with calf thymus DNA is hardly distinguis hable from that obtained with poly(dG-dC)-poly(dG-dC), suggesting a bi nding of PZE to G-C rich regions. (C) 1997 Elsevier Science S.A.