Head-to-head bis-Hairpin Polyamide Minor Groove Binders and Their Conjugates with Triplex-forming Oligonucleotides: Studies of Interaction with Target Double-stranded DNAстатья
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Аннотация:Two hairpin hexa(N-methylpyrrole)carboxamide DNA minor groove binders (MGB) were
linked together via their N-termini in head-to-head orientation. Complex formation between
these bis-MGB conjugates and target DNA has been studied using DNase I footprinting,
circular dichroism, thermal dissociation, and molecular modeling. DNase I footprint
revealed binding of these conjugates to all the sites of 492 b.p. DNA fragment containing
(A/T)nXm(A/T)p sequences, where n>3, p>3; m=1,2; X = A,T,G, or C. Binding affinity
depended on the sequence context of the target. CD experiments and molecular modeling
showed that oligo(N-methylpyrrole)carboxamide moieties in the complex form two short
antiparallel hairpins rather than a long parallel head-to-head hairpin. Binding of bis-MGB
also stabilized a target duplex thermodynamically. Sequence specificity of bis-MGB/DNA
binding was validated using bis-conjugates of sequence-specific hairpin (N-methylpyrrole)/
(N-methylimidazole) carboxamides.