Formation of nucleosomes does not suppress interaction of a DNA fragment with an alkylating derivative of a pyrimidine oligonucleotide.

Oligonucleotide derivatives capable of binding to specific nucleic acids are considered as potential therapeutic agents, exerting their action at the level of genome functioning (Hélène, 1991; Knorre et al., 1993). A straightforward approach to targeting DNA is based on using oligonucleotides capable of binding to oligopurine-oligopyrimidine sequences by formation of triple-strand structures. We report results of experiments on sequence-specific chemical modification of a 490-bp fragment of pfosCAT plasmid, containing the promoter segment of the c-fos gene using 4-(N-2-chloroethyl-N-methylamino)-benzylphosphamide derivatives of a homopyrimidine 14-mer oligonucleotide. It was shown that in both the free DNA and the DNA involved in nucleosome structure, reaction occurred with similar efficiency at the target guanosine residue G404.