Drug binding to human serum albumin: Abridged review of results obtained with high‐performance liquid chromatography and circular dichroism

Abstract

The drug binding to plasma and tissue proteins are fundamental factors in determining the overall pharmacological activity of a drug. Human serum albumin (HSA), together with a 1 -acid glycoprotein (AGP), are the most important plasma proteins, which act as drug carriers, with drug pharmacokinetic implications, resulting in important clinical impacts for drugs that have a relatively narrow therapeutic index. This review focuses on the combination of biochromatography and circular dichroism as an effective approach for the characterization of albumin binding sites and their enantioselectivity. Furthermore, their applications to the study of changes in the binding properties of the protein arising by the reversible or covalent binding of drugs are discussed, and examples of physiological relevance reported. Perspectives of these studies reside in supporting the development of new drugs, which require miniaturization to facilitate the screening of classes of compounds for their binding to the target protein, and a deeper characterization of the mechanisms involved in the molecular recognition processes.

Why mammals more susceptible to the hepatotoxic microcystins than fish: evidences from plasma and albumin protein binding through equilibrium dialysis

“…As a result, a full characterization of the binding property to plasma proteins has become essential for understanding the pharmacokinetic and toxicological profile of a drug. Among various plasma proteins, serum albumin is the predominant plasma protein, comprising more than half of the total protein in normal serum (Kanakis et al 2006;Ascoli et al 2006). It often contributes significantly towards the total binding of basic drugs in plasma (Kurtzhals et al 1995;Dennis et al 2002;Yuwiler et al 2006).…”

Ibuprofen modulates allosterically NO dissociation from ferrous nitrosylated human serum heme-albumin by binding to three sites

“…Bulky heterocyclic molecules (e.g., warfarin) bind preferentially to Sudlow's site I, whereas Sudlow's site II is preferred by aromatic carboxylates with an extended conformation (e.g., ibuprofen) [1][2][3][5][6][7][8][9][10][11][12][13][14]26,[31][32][33][34][35][36].…”

Abacavir and warfarin modulate allosterically kinetics of NO dissociation from ferrous nitrosylated human serum heme-albumin

“…Human serum albumin (HSA), the most prominent protein in plasma, provides a depot and carrier for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders harmless potential toxins transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and displays (pseudo-)enzymatic properties [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

“…Heme propionates point towards the interface between domains I and III and are stabilized by salt bridges with His146 and Lys190 [18,19]. Bulky heterocyclic molecules bind preferentially to Sudlow's site I, whereas Sudlow's site II is preferred by aromatic carboxylates with an extended conformation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]20].…”