Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: derivatives of oligo-1,3-thiazolecarboxamides.
Antisense Nucleic Acid Drug Dev
; 11(3): 137-47, 2001 Jun.
Article
in En
| MEDLINE
| ID: mdl-11446589
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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Topoisomerase I Inhibitors
Limits:
Humans
Language:
En
Journal:
Antisense Nucleic Acid Drug Dev
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
FARMACOLOGIA
Year:
2001
Document type:
Article