title: Hairpin polyamides that use parallel and antiparallel side-by-side peptide motifs in binding to DNA.
abstract: Pt-bis-netropsin is a synthetic sequence-specific DNA-binding ligand comprizing two netropsin-like fragments which are linked in a tail-to-tail manner via a cis-diammineplatinum (II) residue. The CD studies and thermodynamic characterization of the DNA-binding properties exhibited by this compound reveal that it forms two types of complexes with poly[d(AT)].poly[d(AT)] and DNA oligomers containing nucleotide sequences 5'-CC(TA)n CC-3', with n = 4, 5 and 6. The first type corresponds to the binding of Pt-bis-netropsin in the extended conformation and is characterized by the saturating ratio of one bound Pt-bis-netropsin molecule per 9 AT-base pairs. The second type of the complex corresponds to the binding of Pt-bis-netropsin to DNA in the folded hairpin form. The binding approaches saturation level when one Pt-bis-netropsin molecule is bound per four or five AT-base pairs. The hairpin form of Pt-bis-netropsin complex is built on the basis of parallel side-by-side peptide motif which is inserted in the minor DNA groove. The CD spectral profiles reflecting the binding of Pt-bis-netropsin in the hairpin form are different from those observed for binding of another bis-netropsin with the sequence Lys-Gly-Py-Py-Gly-Gly-Gly-Py-Py-Dp, where Py is a N-propylpyrrole amino acid residue and Dp is a dimethylaminopropylamino residue. The hairpin form of this bis-netropsin is formed on the basis of antiparallel side-by-side peptide motif. The CD spectra obtained for complexes of this polyamide in the hairpin form with poly[d(AT)].poly[d(AT)] exhibit positive CD band with a peak at 325 nm, whereas the CD spectral profiles for the second complex of Pt-bis-Nt with poly[d(AT)].poly[d(AT)] and short DNA oligomers have two intense positive CD bands near 290 nm and 328 nm. This reflects the fact that two bis-netropsins use different structural motifs on binding to DNA in the hairpin form.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: A N
authors.initials: AN
authors.lastname: Surovaya
authors.forename: G
authors.initials: G
authors.lastname: Burckhardt
authors.forename: S L
authors.initials: SL
authors.lastname: Grokhovsky
authors.forename: E
authors.initials: E
authors.lastname: Birch-Hirschfeld
authors.forename: G V
authors.initials: GV
authors.lastname: Gursky
authors.forename: C
authors.initials: C
authors.lastname: Zimmer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004355:Drug Stability; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011067:Poly dA-dT / Q000737:chemistry; D011487:Protein Conformation; D011758:Pyrroles; D013816:Thermodynamics
chemical_list: D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011758:Pyrroles; D011067:Poly dA-dT; D004247:DNA