The role of the gulose-mannose part of bleomycin in activation of iron-molecular oxygen complexes.
A comparison of the complexing properties of metal ions and O2 activation by bleomycin-A2 (BLM-A2) and deglyco-BLM-A2 is presented. Deglyco-BLM-A2 is obtained from the parent derivative by HF cleavage of the sugar moiety followed by h.p.l.c. purification. Complexing of Cu(II) and Fe(III) is studied by using c.d. and e.s.r. spectroscopy. Spin-trapping experiments in the presence of phenyl N-t-butylnitrone indicated lower production of free radicals by deglyco-BLM-A2. Finally, a proposal is made to explain this discrepancy, focusing on the probable role of the gulose-mannose moiety acting as a protecting pocket, comparable with the pocket and picket-fence porphyrins described for haemoproteins.
Kénani
A
A
Unité INSERM N. 16, Lille, France.
Bailly
C
C
Helbecque
N
N
Catteau
J P
JP
Houssin
R
R
Bernier
J L
JL
Hénichart
J P
JP
D001761:Bleomycin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006601:Hexoses; D007501:Iron / Q000378:metabolism*; D046911:Macromolecular Substances; D008358:Mannose; D013058:Mass Spectrometry; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*
D005609:Free Radicals; D006601:Hexoses; D046911:Macromolecular Substances; D001761:Bleomycin; C057406:gulose; D003300:Copper; D007501:Iron; D008358:Mannose; D010100:Oxygen