title: Design of distamicin analogues to probe the physical origin of the antiparallel side by side oligopeptide binding motif in DNA minor groove recognition.
abstract: Oligopeptides distamycin and its analogues can bind cooperatively to the minor groove of certain DNA sequences in a closely compacted antiparallel side by side motif, where the positively charged ends are located in the carboxyl termini of such peptidic structures. In order to dissect its physical underpinning, the role of charge in maintaining the integrity of this novel motif is explored by using three judiciously designed distamycin analogues possessing either no charge or with charge ends located in the amino termini. Preliminary experiments by CD and ethidium fluorescence displacement suggested that the charge plays an role in influencing the degree of binding cooperativity as well as binding strength, although qualitatively the dimeric binding remains cooperative.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004214:Distamycins / Q000737:chemistry*; D015195:Drug Design; D066298:In Vitro Techniques; D015335:Molecular Probes; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D011067:Poly dA-dT / Q000737:chemistry
chemical_list: D004214:Distamycins; D015335:Molecular Probes; D009842:Oligopeptides; D011067:Poly dA-dT; D004247:DNA