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Structural analyses of metallodrug/β-lactoglobulin adducts for rational design of new biomaterials
* 1 , 1 , 2
1  Department of Chemical Sciences, University of Naples Federico II, Naples, Italy
2  Department of Chemistry "Ugo Schiff", University of Florence, FI, Italy


β-lactoglobulin (BLG) is a whey carrier protein of 18.4 kDa. This protein is a good system for the preparation of micro- or nanoparticles for pharmaceutical industry because of its high solubility, safe status, biodegradable nature, gel forming ability, abundance, stability at acidic pH and against gastric pepsin. It has been shown that BLG can bind anticancer Pt-based drugs and that BLG–pectin nanoparticles can transfer cytotoxic Pt compounds to cancer cells.

To study the molecular basis of the Pt-based drug recognition by BLG, we have analyzed the interaction of this protein with two extensively used anticancer metallodrugs, i.e. cisplatin and oxaliplatin, both in solution and at solid state. Structural data reveal that cisplatin binds BLG coordinating Met7, His146 and Lys8 side chains, without affecting the overall 3D structure. The molecular structure of the adduct formed upon reaction of oxaliplatin with BLG suggests the existence of a single Pt binding site. Circular Dichroism analyses reveal that the overall structure of the protein is not altered upon interaction with the metal compound.

These results suggest that BLG could act as a carrier for anticancer metallodrugs and open the way for a rational design of new biomaterials based on metallodrug/β-lactoglobulin adduct nanoparticles.

Keywords: Metallodrugs, metal-protein interactions, anticancer agents