Dv. Bugreev et al., Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: Derivatives of oligo-1,3-thiazolecarboxamides, ANTISENSE N, 11(3), 2001, pp. 137-147
A series of novel thiazole-containing oligopeptides (oligo-1,3-thiazolecarb
oxamides) interesting specifically with the minor groove of DNA was shown t
o inhibit human DNA topoisomerase I (topo I). Inhibitory effects of thiazol
e-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 natu
ral antibiotic, distamycin A containing pyrrole rings. The structure of var
ious 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 (ds-DNA
), and the majority of TCO analyzed were more effective in binding with dsD
NA than distamycin A. Possible reasons for the different effects of distamy
cin A and TCO on the reaction of relaxation catalyzed by topo I are discuss
ed.