Binding of a hairpin polyamide in the minor groove of DNA: sequence-specific enthalpic discrimination.
Hairpin polyamides are synthetic ligands for sequence-specific recognition in the minor groove of double-helical DNA. A thermodynamic characterization of the DNA-binding properties exhibited by a six-ring hairpin polyamide, ImPyPy-gamma-PyPyPy-beta-Dp (where Im = imidazole, Py = pyrrole, gamma = gamma-aminobutyric acid, beta = beta-alanine, and Dp = dimethylaminopropylamide), reveals an approximately 1-2 kcal/mol greater affinity for the designated match site, 5'-TGTTA-3', relative to the single base pair mismatch sites, 5'-TGGTA-3' and 5'-TATTA-3'. The enthalpy and entropy data at 20 degrees C reveal this sequence specificity to be entirely enthalpic in origin. Correlations between the thermodynamic driving forces underlying the sequence specificity exhibited by ImPyPy-gamma-PyPyPy-beta-Dp and the structural properties of the heterodimeric complex of PyPyPy and ImPyPy bound to the minor groove of DNA provide insight into the molecular forces that govern the affinity and specificity of pyrrole-imidazole polyamides.
Pilch
D S
DS
Department of Chemistry, Rutgers-State University of New Jersey, New Brunswick 08903, USA.
Poklar
N
N
Gelfand
C A
CA
Law
S M
SM
Breslauer
K J
KJ
Baird
E E
EE
Dervan
P B
PB
D000577:Amides / Q000737:chemistry*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000577:Amides; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D004247:DNA