Is the bithiazole moiety of bleomycin a classical intercalator?
Bleomycin is a widespread anticancerous drug, the biological activity of which having been extensively studied. Its metal ion-chelating portion has been shown to cleave DNA whereas the role of the bithiazole moiety is still questionable. In order to elucidate this problem some 2', 4-disubstituted bithiazoles structurally related to the "tripeptide S" moiety of bleomycin were synthesized and their interaction with DNA was studied using delta Tm, fluorescence, EPR and viscometry techniques. The results of delta Tm and fluorescence quenching determinations were in favour of a binding of the bithiazole part by an intercalation process. Nevertheless, the use of the spin-label probes indicated only a partial intercalation of the ring between the base-pairs. Moreover, viscometry data which clearly exhibited a slight decrease of DNA length in the presence of bithiazole derivative led to the proposal of a binding model involving a partial insertion of a thiazole ring which wedges in between the bases at a bending point of DNA.
J P
JP
Hénichart
J L
JL
Bernier
N
N
Helbecque
R
R
Houssin
D000818:Animals; D001482:Base Composition; D001761:Bleomycin / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D007364:Intercalating Agents; D009691:Nucleic Acid Denaturation; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013844:Thiazoles; D013950:Thymus Gland
D007364:Intercalating Agents; D013844:Thiazoles; D001761:Bleomycin; D004247:DNA