title: Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: derivatives of oligo-1,3-thiazolecarboxamides.
abstract: A series of novel thiazole-containing oligopeptides (oligo-1,3-thiazolecarboxamides) interesting specifically with the minor groove of DNA was shown to inhibit human DNA topoisomerase I (topo I). Inhibitory effects of thiazole-containing oligopeptides (TCO) increase with the number of thiazole units in such compounds. Inhibitory properties of TCO containing 3 or 4 thiazole units were shown to be 3-10 times better than those of the well-known natural antibiotic, distamycin A containing pyrrole rings. The structure of various additional groups attached to the N-terminus and C-terminus of TCO had no significant effect on TCO interaction with the complex of DNA and topo I. TCO were shown to be capable of binding with double-stranded DNA (dsDNA), and the majority of TCO analyzed were more effective in binding with dsDNA than distamycin A. Possible reasons for the different effects of distamycin A and TCO on the reaction of relaxation catalyzed by topo I are discussed.
authors.affiliation: Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences.
authors.forename: D V
authors.initials: DV
authors.lastname: Bugreev
authors.forename: E L
authors.initials: EL
authors.lastname: Vasyutina
authors.forename: V A
authors.initials: VA
authors.lastname: Ryabinin
authors.forename: A N
authors.initials: AN
authors.lastname: Sinyakov
authors.forename: V N
authors.initials: VN
authors.lastname: Buneva
authors.forename: G A
authors.initials: GA
authors.lastname: Nevinsky
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004214:Distamycins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
chemical_list: D004214:Distamycins; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D013844:Thiazoles; D059004:Topoisomerase I Inhibitors; D004247:DNA