BINDING OF A HAIRPIN POLYAMIDE IN THE MINOR-GROOVE OF DNA - SEQUENCE-SPECIFIC ENTHALPIC DISCRIMINATION

Hairpin polyamides are synthetic ligands for sequence-specific recogni tion in the mirror groove of double-helical DNA. A thermodynamic chara cterization of the DNA-binding properties exhibited by a six-sing hair pin polyarmide, ImPyPy-gamma-PyPyPy-beta-Dp (where Im = imidazole, Pv = pyrrole, gamma = gamma-amimobutyric acid, beta = beta-alaniae, and D p = dimethylaminopropylamide), reveals an approximate to 1-2 kcal/mol greater affinity for the designated match site, 5'-TGTTA-3' relative t o the single base pair mismatch sites, 5'-TGGTA-3' and 5'-TATTA-3'. Th e enathalpy and entropy data at 20 degrees C reveal this sequence spec ificity to be entirely enthalpic in origin. Correlations between the t hermodynamic driving forces underlying the sequence specificity exhibi ted by Im-PyPy-gamma-PyPyPy-beta-Dp and the structural properties of t he heterodimeric complex of PyPyPy and ImPyPy bound to the minor grope of DNA provide insight into the molecular forces that govern the affi nity and specificity of pyrrole-imidazole polyamides.