A. Skorobogaty

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Oligopeptides have been synthesized that are structurally related to the antiviral antitumor antibiotic netropsin, but in which each of the pyrrole units is successively replaced by an imidazole moiety, as well as their di- and triimidazole-containing counterparts. These compounds bind to duplex DNA with constants in the range (1.06-1.98) X 10(6) M-1 but(More)
The DNA-sequence specificity of daunomycin was investigated by DNase I footprinting and an E. coli RNA polymerase transcription-inhibition assay. The 5'-CA sequence was identified as being the highest affinity binding site, although other modest affinity (5'-GC, CG, CT, TC, AC) and poor affinity sites (5'-AA, AT, TA) were also observed. The preference of(More)
A new bis-daunomycin has been synthesized and characterized by 13C-n.m.r. and reversed-phase h.p.l.c. The compound was found to be highly self-associated in aqueous solution and to bis-intercalate into DNA with a residence time about 200-fold greater than the parent compound daunomycin. Although the bis-daunomycin and its parent congener were taken up by(More)
The ability of a group of water-soluble metalloporphyrins to cleave DNA has been investigated. Incubation of Mn3+, Fe3+, or Co3+ complexes of meso-tetrakis(N-methyl-4-pyridiniumyl)porphine (H2T4MPyP) with DNA in the presence of ascorbate, superoxide ion, or iodosobenzene results in DNA breakage. Comparisons between the rates of porphyrin autodestruction(More)
The sequence specificity of daunomycin was assessed using competition equilibrium dialysis, DNAse I footprinting and an E. coli RNA polymerase transcription inhibition assay; similar studies were performed on adriamycin and a new bis-intercalating daunomycin dimer. The results clearly demonstrate that the highest affinity sites are CA for daunomycin and(More)
A series of metalloporphyrins linked through basic chains to certain DNA interactive groups has been synthesized. Several of these agents reproduce the characteristic properties of the antitumor glycopeptide bleomycin, including the oxygen-mediated scission of DNA in the presence of thiols, antibiobic activity under aerobic conditions, and activity against(More)
A system comprised of a linear scanning microdensitometer interfaced to a personal computer has been developed to facilitate analysis of ligand-DNA footprinting autoradiograms. The system, which can be used to record density and sequence information from autoradiographic films, enables the user to relate the area under an autoradiographic band to the(More)
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