[Effect of a copper-chelating peptide on the anticancer activity of anthraquinones].
Pseudopeptides incorporating a polyhydroxyanthraquinone ring related to the nuclei of the antitumor drug Mitoxantrone and a peptidic metal-chelating moiety Gly-His-Lys (GHK), have been synthesized. The goal was to conjugate the redox effects of a quinone ring with the iron chelating properties of the peptide in order to generate free radical species capable of damaging DNA. DHQ-GHK has a moderate affinity for DNA but causes precipitation of filaments. Electron microscopy shows a loop-making organization, DNA molecules having a lengthening superior to 50% as compared to control supercoiled DNA, the inside of these loops looks free of granular deposit. The peptidic moiety forms a complex with copper when the ratio Cu/P is lower than 0.2. This cupric complex catalyses the formation of free radicals and the cleavage of the DNA double strand. A new synthesis is described involving the addition of a space arm between the anthraquinonic nucleus and copper chelating compounds to obtain derivates disubstituted by different chelators.
Morier-Teissier
E
E
Unité 16, INSERM, Lille, France.
D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction
D000880:Anthraquinones; D000970:Antineoplastic Agents; D002614:Chelating Agents; D009842:Oligopeptides; C020905:glycyl-histidyl-lysine; D003300:Copper; D004247:DNA
Apport d'un peptide chélateur du cuivre à l'activité anticancéreuse des anthraquinones.