title: Alternative heterocycles for DNA recognition: a 3-pyrazole/pyrrole pair specifies for G.C base pairs.
abstract: Synthetic ligands comprising three aromatic amino acids, pyrrole (Py), imidazole (Im), and hydroxypyrrole (Hp), specifically recognize predetermined sequences as side-by-side pairs in the minor groove of DNA. To expand the repertoire of aromatic rings that may be utilized for minor groove recognition, three five-membered heterocyclic rings, 3-pyrazolecarboxylic acid (3-Pz), 4-pyrazolecarboxylic acid (4-Pz), and furan-2-carboxylic acid (Fr), were examined at the N-terminus of eight-ring hairpin polyamide ligands. The DNA binding properties of 3-Pz, 4-Pz, and Fr each paired with Py were studied by quantitative DNase I footprinting titrations on a 283 bp DNA restriction fragment containing four 6-bp binding sites 5'-ATNCCTAA-3' (N = G, C, A, or T; 6-bp polyamide binding site is underlined). The pair 3-Pz/Py has increased binding affinity and sequence specificity for G.C bp compared with Im/Py.
authors.affiliation: The Beckman Institute, California Institute of Technology, Pasadena 91125, USA.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Zhan
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D018983:DNA Footprinting; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010957:Plasmids; D011720:Pyrazoles / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D006571:Heterocyclic Compounds; D011720:Pyrazoles; D011758:Pyrroles; D004247:DNA