Oxidation-reduction reactions of iron bleomycin in the absence and presence of DNA.
Using the pulse radiolysis technique, we have demonstrated that bleomycin-Fe(III) is stoichiometrically reduced by CO2- to bleomycin-Fe(II) with a rate of (1.9 +/- 0.2) x 10(8) M-1s-1. In the presence of calf thymus DNA, the reduction proceeds through free bleomycin-Fe(III) and the binding constant of bleomycin-Fe(III) to DNA has been determined to be (3.8 +/- 0.5) x 10(4) M-1. It has also been demonstrated that in the absence of DNA O2- reacts with bleomycin-Fe(III) to yield bleomycin-Fe(II)O2, which is in rapid equilibrium with molecular oxygen, and decomposes at room temperature with a rate of (700 +/- 200) s-1. The resulting product of the decomposition reaction is Fe(III) which is bound to a modified bleomycin molecule. We have demonstrated that during the reaction of bleomycin-Fe(II) with O2, modification or self-destruction of the drug occurs, while in the presence of DNA no destruction occurs, possibly because the reaction causes degradation of DNA.
Goldstein
S
S
Department of Physical Chemistry, Hebrew University of Jerusalem, Israel.
Czapski
G
G
D001761:Bleomycin / Q000378:metabolism* / Q000031:analogs & derivatives; D002245:Carbon Dioxide / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005720:Gamma Rays; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis; D013053:Spectrophotometry
C023503:iron bleomycin; D001761:Bleomycin; D002245:Carbon Dioxide; D003300:Copper; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron