Human serum transferrin (hTF) is an 80 kDa single-chain protein formed by two lobes (N and C), each containing a Fe³⁺ binding site. Depending on the number of Fe³⁺ bound, hTF exists in different forms. In addition to the apo- and holo-hTF, containing respectively no or two ferric ions, hTF can also occur in two monoferric forms. In these latter, only one Fe³⁺ is bound either to N- (Fe_N-hTF) or C-lobe (Fe_C-hTF).

As a consequence of the over expression of transferrin receptor on cancer cells, hTF has been proposed as a potential anticancer drug carrier. It has also been demonstrated that hTF can bind the anticancer agent cisplatin ([cis-Pt(NH₃)₂Cl₂]) and selectively deliver it to cancer cells. Although numerous studies have been conducted to determine the molecular mechanism of cisplatin binding to hTF, there are still divergent opinions on the cisplatin binding sites of hTF. This is mainly due to the substantial lack of direct structural information on the adducts formed by cisplatin and the different hTF forms.

In this context, we recently solved, for the first time, the crystallographic structures of the adducts formed upon reaction of the cisplatin with apo-hTF or Fe_C-hTF. The two structures show a different number of Pt-binding sites and could help to clarify the reactivity of the cisplatin towards the different forms of hTF.