Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

Human serum albumin: from bench to bedside.

Albumin-based nanoparticles as potential controlled release drug delivery systems.

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism underlying this cytoprotective effect relies on the ability of HO-1 to catabolize free heme and prevent it from sensitizing cells to undergo programmed cell death. This cytoprotective effect inhibits the pathogenesis of a variety of immune-mediated inflammatory diseases.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.pharmtox.010909.105600

Mechanisms of Cell Protection by Heme Oxygenase-1

Human serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized

https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1080/15216540500404093

The extraordinary ligand binding properties of human serum albumin

Human serum albumin (HSA), the most prominent protein in plasma, is best known for its extraordinary ligand binding capacity. The three homologous domains of HSA (labeled I, II, and III), each in turn composed of two subdomains (named A and B), give rise to the three-dimensional structure of HSA. This flexible structural organization allows the protein structure to adapt to a variety of ligands. As conformational adaptability of HSA extends well beyond the immediate vicinity of the binding site(s), cooperativity and allosteric modulation arise among binding sites; this makes HSA similar to a multimeric protein. Although kinetic and thermodynamic parameters for ligand binding to HSA calculated by quantitative structure-activity relationship models are in excellent agreement with those obtained in vitro, cooperative and allosteric equilibria between different binding sites and competition between drugs or between drugs and endogenous ligands make difficult the interpretation of HSA binding properties in vivo. Binding of exogenous and endogenous ligands to HSA appears to be relevant in drug therapy and management. Here, the allosteric modulation of drug binding to HSA is briefly reviewed.

Allosteric modulation of drug binding to human serum albumin.

Flavonoid binding to human serum albumin.

Human serum albumin (HSA), the most prominent protein in blood plasma, is able to bind a wide range of endogenous and exogenous compounds. Among the endogenous ligands, HSA is a significant transporter of heme, the heme−HSA complex being present in blood plasma. Drug binding to heme−HSA affects allosterically the heme affinity for HSA and vice versa. Heme−HSA, heme, and their complexes with ibuprofen have been characterized by electronic absorption, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy. Comparison of the results for the heme and heme−HSA systems has provided insight into the structural consequences on the heme pocket of ibuprofen binding. The pentacoordinate tyrosine-bound heme coordination of heme−HSA, observed in the absence of ibuprofen, becomes hexacoordinate low spin upon ibuprofen binding, and heme dissociates at increasing drug levels. The electronic absorption spectrum and ν(Fe−CO)/ν(CO) vibrational frequencies of the CO−heme−HSA−ibuprofen complex, together with ...

Gabriella Fanali

Papers

Human serum albumin: from bench to bedside.

The extraordinary ligand binding properties of human serum albumin

Allosteric modulation of drug binding to human serum albumin.

Flavonoid binding to human serum albumin.

Ibuprofen Induces an Allosteric Conformational Transition in the Heme Complex of Human Serum Albumin with Significant Effects on Heme Ligation