Structural studies of human transferrin for its potential application as a drug delivery system

The present work explores the proposal of using an endogenous transport molecule, human serum transferrin, as a highly specific drug delivery system, due to its receptor-mediated transcytosis mechanism [1] . Human serum transferrin is a ~80 kDa bilobular glycoprotein that transits the blood plasma, whose function is to transport iron from its absorption site towards every cell in the organism, by the coordination of the metallic ion with 4 residues located in the inter-domain region of each lobe. Both lobes are linked by an unstructured linker peptide, which makes the protein highly flexible [2-3]. Thus, this work is focused on studying the conformational changes of this protein throughout its transport mechanism, mainly by two structural resolution techniques, small angle X-ray scattering (SAXS), and protein X-ray crystallography, to explore potential binding sites. The results obtained so far have shown the coexistence of three main conformations in different physiologically relevant pH conditions, as well as a particular sensitivity to changes in the medium conditions, namely pH