5-S-cysteinyldopa, a diffusible product of melanocyte activity, is an efficient inhibitor of hydroxylation/oxidation reactions induced by the Fenton system.
Interest in 5-S-cysteinyldopa (5-S-CD), a major excretion product of normal and malignant melanocytes, has traditionally concentrated on its significance as a biosynthetic precursor of pheomelanins, the characteristic pigments of red hair, and as a specific biochemical marker for monitoring melanoma progression. The present study shows that 5-S-CD is a potent inhibitor of hydroxylation/oxidation reactions mediated by hydrogen peroxide and the Fe2+/EDTA complex under both aerobic and anaerobic conditions. The inhibitory effect of 5-S-CD, as determined by the deoxyribose and salicylic acid assays in phosphate buffer (pH 7.4), is much stronger than that of dopa, acetylsalicylic acid and mannitol, increases with increasing ligand-to-metal ratio, and is inversely proportional to the concentration of EDTA present in the Fenton system. Spectrophotometric evidence and competition experiments indicate that 5-S-CD forms a chelate complex with ferric ions (lambda max = 500 nm at pH 7.4), which may account for both an altered production of hydroxyl radicals by the Fenton reagent and a site-specific localization of oxidative damage on the chelate complex itself.
Napolitano
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Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
Memoli
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S
Nappi
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AJ
d'Ischia
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M
Prota
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G
D000332:Aerobiosis; D000693:Anaerobiosis; D001894:Borohydrides / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003548:Cysteinyldopa / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006900:Hydroxylation / Q000187:drug effects; D007502:Iron Chelating Agents / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D012459:Salicylates / Q000378:metabolism; D020156:Salicylic Acid
D001894:Borohydrides; D002614:Chelating Agents; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D012459:Salicylates; D003548:Cysteinyldopa; D004295:Dihydroxyphenylalanine; C025364:sodium borohydride; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D020156:Salicylic Acid