Correlation of local effects of DNA sequence and position of β-alanine inserts with polyamide-DNA complex binding affinities and kinetics.

摘要: To improve our understanding of the effects β-alanine (β) substitution and number heterocycles on DNA binding affinity selectivity, we investigated interactions an eight-ring hairpin polyamide (PA) two β derivatives as well a six-heterocycle analogue with their cognate sequence, 5'-TGGCTT-3'. Binding selectivity have been five mutant DNAs. A set powerful complementary methods employed for both energetic structural evaluations: UV melting, biosensor surface plasmon resonance, isothermal titration calorimetry, circular dichroism, ligation ladder global structure assay. The reduced in six-ring PA weakens affinity; however, smaller aggregates significantly less than larger PAs allows us to obtain thermodynamics. PA-DNA enthalpy is large negative ΔC(p) primary driving component Gibbs free energy. complete SPR results clearly show that substitutions can substantially weaken position-dependent manner. More importantly, changes DNAs further confirm interaction affinity. Comparison sequences also shows different effect recognition T·A versus A·T base pairs. mutations single position tell clear very important story about sequence-dependent DNA.