Bugreev D V, Vasyutina E L, Ryabinin V A, Sinyakov A N, Buneva V N, Nevinsky G A
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of the Russian Academy of Sciences.
Antisense Nucleic Acid Drug Dev. 2001 Jun;11(3):137-47. doi: 10.1089/108729001300338663.
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.
