INTERACTION OF THE ANTITUMORAL DRUG PAZELLIPTINE WITH POLYNUCLEOTIDES- A SUBPICOSECOND TRANSIENT ABSORPTION STUDY

The flat heterocyclic antitumoral drug pazelliptine (PZE) strongly int eracts with nucleic acids. The transient absorption spectra of PZE/pol ynucleotide complexes have been investigated with subpicosecond time r esolution on a large spectral range, 400-850 nm. The relaxation dynami cs are found to vary widely depending upon the type of polynucleotide in which PZE has been inserted. For fully protonated PZE and for PZE c omplexed to poly(dA-dT)-poly(dA-dT), a similar fast spectral relaxatio n was detected and assigned to a deprotonation of the excited singlet state of the drug. In the case of the PZE/poly(dG-dC)-poly(dG-dC) comp lex, the evolution of the transient absorption spectra suggests that t here are at least two different drug binding sites. The kinetics of th e differential absorption reveals the activation of a radiationless tr ansition S-1-->S-0 upon PZE association to poly(dG-dC)-poly(dG-dC). Th e possible mechanism of this fast molecular process is discussed in co nnection with previously reported results on heterocycle-nucleotide in teractions.