DNA cleavage by Cu(II)-desferal: identification of C1'-hydroxylation as the initial event for DNA damage

Abstract

Desferal, a siderophore of microbial origin is the only drug currently used for clinical treament of a genetic disorder, thalassemia. By using a combinationof HPLC and ³¹P-NMR, it is demonstrated that the Cu complex of desferal cleaves DNA, the primary site of hydroxyl radical attack being the sugar C1' in the minor groove, which leads to production of 5-methylene furanone. While no C5'-oxidatino was observed, a minor process involving C4'-attack accompanies the above cleavage path. The oxidative cleavage of DNA observed with CuDFO may have implications in the emerging applications of desferal as a drug delivery agent and an antimalarial.