Ricerc@Sapienza

Human Serum Albumin (HSA) is the most abundant protein in body fluids, where it serves as a carrier and depot for many molecules that can interact with the multiple binding sites located in its three-domain structure. The protein is also known to undergo conformational transitions towards partially unfolded forms triggered by acidification below pH 4.5. However, the potential loss of affinity for the ligands related to such structural variations has not be thoroughly elucidated so far. We propose to use a time-dependent pH scanning protocol to monitor the process of acid unfolding of complexes of HSA with specific spectroscopically active ligands, to verify the possible release phenomena determined by the protein conformational variations. Clarifying the interplay between the protein conformational transitions in acid conditions and the ligand binding/release equilibria could pave the way to the use of albumin as a specific pH-dependent carrier in nanotechnological formulations.