An overview of albumin and alpha-1-acid glycoprotein main characteristics: highlighting the roles of amino acids in binding kinetics and molecular interactions

Abstract Although Albumin (ALB) and alpha-1-acid glycoprotein (AGP) have distinctive structural and functional characteristics, they both play a key role in binding a large variety of endogenous and exogenous ligands. An extensive binding to these plasma proteins could have a potential impact on drugs disposition (e.g. bioavailability, distribution and clearance), on their innocuity and their efficacy. This review summarizes the common knowledge about the structural and molecular characteristics of both ALB and AGP in humans, and about the most involved amino acids in their high-affinity binding pockets. However, the variability in residues found in binding pockets, for the same species, allows each plasma protein to interact differently with the ligands. The protein-ligand interaction influences differently the disposition of drugs that bind to either of these plasma proteins. The content of this review is useful for the design of new drug entities with high-binding characteristics, in qualitative and quantitative modelling (e.g. in vitro-in vivo extrapolations, 3D molecular docking, interspecies extrapolations), and for other interdisciplinary research.