title: Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif.
abstract: Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kelly
authors.forename: E E
authors.initials: EE
authors.lastname: Baird
authors.forename: P B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D000596:Amino Acids; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D007093:Imidazoles; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011758:Pyrroles; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000596:Amino Acids; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D011758:Pyrroles; D004247:DNA; C096654:N-methylpyrrole; C018100:1-methylimidazole