Loris Leboffe, Alessandra di Masi*, Fabio Polticelli, Viviana Trezza and Paolo Ascenzi Pages 4907 - 4931 ( 25 )
Background: Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.
Objective: In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.
Conclusion: As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.
Human serum albumin, drug carrier, drug recognition, structural basis, allosteric modulation of drug binding, competitive modulation of drug binding.
Department of Sciences, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Department of Sciences, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Department of Sciences, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Department of Sciences, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, I- 00146 Roma