INTERACTION OF DERIVATIVES OF SHORT OLIGO NUCLEOTIDES WITH NUCLEIC-ACIDS - VII - EFFECT OF CONFORMATIONAL-CHANGES IN THE DUPLEX STRUCTURE ON SITE-SPECIFICITY AND EFFICIENCY OF MODIFICATION OF TARGET DNA BY ALKYLATING OLIGONUCLEOTIDE DERIVATIVES
Dv. Pyshnyi et al., INTERACTION OF DERIVATIVES OF SHORT OLIGO NUCLEOTIDES WITH NUCLEIC-ACIDS - VII - EFFECT OF CONFORMATIONAL-CHANGES IN THE DUPLEX STRUCTURE ON SITE-SPECIFICITY AND EFFICIENCY OF MODIFICATION OF TARGET DNA BY ALKYLATING OLIGONUCLEOTIDE DERIVATIVES, Bioorganiceskaa himia, 24(2), 1998, pp. 132-138
The modification of a target DNA by alkylating oligonucleotide derivat
ives possessing various capacities for complex formation was studied.
The binding properties of oligonucleotides were changed either by incr
easing their length (tetra-, octa-, and dodecamers) or by introducing
a point substitution and/or an N-(2-hydroxyethylphenazinium) residue.
It was found that conformational changes occurring in the structure of
the target reagent complex upon elevating the reaction temperature af
fect the efficiency and site-specificity of the alkylation. In the cas
e of complete saturation of the target with the reagent, an increase i
n the hybridization ability of the reagent reduced the efficiency of t
he target modification. It was found that the modification by the tetr
anucleotide reagent (in the presence of an effector adjacent to the 3'
end) occurs exclusively at an intracomplex target base. In the case o
f the dodecamer, which forms a stable, highly cooperative complex with
the target, several bases of the target undergo alkylation, and an in
crease in temperature changes the site-specificity of alkylation. In t
his process, the redistribution of the target modification sites towar
d stronger nucleophilic centers enhances alkylation at temperatures ne
ar the melting temperature of the target dodecanucleotide complex desp
ite a decrease in the extent of target association.