New approach to enhancing the efficiency and specificity of interaction in duplexes by the use of tandem structure

Abstract

Examined in this work is ssDNA recognition by tetranucleotides and their alkylating derivatives in the presence of effectors (native oligonucleotides and their derivatives bearing a duplex stabilizing group such as phenazinium). Though tetranucleotides themselves are not capable of interacting with DNA, the effective site specific DNA recognition by tetranucleolides and their alkylating reagents is caused by the presence of flanking effector pair. The influence of diphenazinium octanucleotide derivatives on the interaction of tetranucleotide or ils reactive derivatives with DNA by far exceeds the influence of native octanucleotides. The level of DNA modification by the alkylating moiety of tetranucleotide depends on hybridization properties of the effector. Tetranucleotide forms complexes with the same DNA-target site with Tm, changing from 0°C to 38°C. Besides, the tetranucleotide reagent modifies that site. The extent of modification varies from 0% to 60%, depending on a type of the effectors used. Having itself several binding sites, the tetranucleotide reagent is made to interact with DNA target exclusively in one binding site determined by the sequence of the flanking effector pair. A new method based on the usage of flanking effector pairs is thus proposed for enhancing the efficiency and specificity of DNA recognition by short oligonucleolides and for discriminating their binding sites.