title: [Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus].
abstract: The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A-T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5'-GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. With further increase in the ratio of the added ligand to the base pairs in CD spectra of complexes with poly[d(A-T)] x poly[d(A-T)], we observed that the maximum wavelength band tend to be shifted towards longer wavelengths, while in the spectral region of 290-310 nm a "shoulder", that was absent in the spectra of the complexes obtained at low polymer coverages by the ligand, appeared. At high molar concentration ratios of ligand to oligonucleotide Pt-bis-Dst can bind to poly[d(A-T)] x poly[d(A-T)] in the form of hairpins or may form associates by the interaction between the distamycin moieties of neighboring molecules of Pt-bis-Dst. The structure of the complexes is stabilized by interactions between pirrolcarboxamide moieties of two molecules of Pt-bis-Dst adsorbed on adjacent overlapping binding sites. These interactions are probably also responsible for the concentration-dependent spectral changes observed during the formation of a complex between Pt-bis-Dst and poly[d(A-T)] x poly[d(A-T)]. Spectral changes are almost absent in binding of Pt-bis-Dst to poly(dA) x poly(dT). Binding of Pt-bis-Dst to duplex O23 reaches saturation if two ligand molecules occur in a duplex that contains a cluster of 18 AT pairs. With increasing the molar concentration ratio of the ligand to the duplex CD spectra undergo concentration-dependent changes similar to those observed during binding of Pt-bis-Dst to poly [d(A-T)] x poly[d(A-T)]. Testing for antiviral efficacy of Pt-bis-Dst showed that the concentration, at which the cytopathic effect produced by the herpes simplex virus in cell culture Vero E6 halved, is equal to 1.5 μg/ml and the selectivity index for evaluating antiviral activity is 65 at a relatively low cytotoxicity. The concentration of Pt-bis-Dst, at which approximately half the cells are killed, is equal to 100 μg/ml.
authors.forename: A N
authors.initials: AN
authors.lastname: Surovaya
authors.forename: N P
authors.initials: NP
authors.lastname: Bazhulina
authors.forename: S Yu
authors.initials: SY
authors.lastname: Lepehina
authors.forename: V L
authors.initials: VL
authors.lastname: Andronova
authors.forename: G A
authors.initials: GA
authors.lastname: Galegov
authors.forename: E D
authors.initials: ED
authors.lastname: Moiseeva
authors.forename: S L
authors.initials: SL
authors.lastname: Grokhovsky
authors.forename: G V
authors.initials: GV
authors.lastname: Gursky
mesh_terms: D002942:Circular Dichroism; D004261:DNA Replication / Q000235:genetics*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D011061:Poly A / Q000737:chemistry / Q000235:genetics; D011071:Poly T / Q000737:chemistry / Q000235:genetics; D018741:Replication Origin / Q000235:genetics*; D018139:Simplexvirus / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D011061:Poly A; D011071:Poly T; C015465:poly(dA)