Promoter scanning of the human COX-2 gene with 8-ring polyamides: Unexpected weakening of polyamide-DNA binding and selectivity by replacing an internal N-Me-pyrrole with β-alanine

▶ We report anomalous DNA binding and recognition of β-alanine substituted polyamides. ▶ We compare thermodynamics/kinetics of DNA binding for β-alanine vs. pyrrole. ▶ Orthogonal methods were used: SPR, fluorescence and quantitative DNA footprinting. ▶ DNA targets included small hairpins, 120-mer dsDNA and 524 bp dsDNA. ▶ A single internal β-alanine weakened DNA binding and decreased binding specificity