Human serum albumin

About: Human serum albumin is a(n) research topic. Over the lifetime, 9402 publication(s) have been published within this topic receiving 269029 citation(s). The topic is also known as: serum albumin & ALB.

Atomic structure and chemistry of human serum albumin.

Abstract: The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and IIIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.

Removal of Fatty Acids from Serum Albumin by Charcoal Treatment

Abstract: The fatty acid contents of 26 different serum albumin preparations representing different species and obtained from various commercial sources have been determined. Some samples had surprisingly little fatty acid contamination, but it was found that other samples contained between 2 and 3 moles of acid per mole of protein, in confirmation of earlier reports. Treatment of these samples with charcoal at low pH resulted in the virtually complete removal of fatty acids. The conditions for such treatment were investigated as a function of the type of fatty acid, pH, and the amount of charcoal required. Charcoal treatment removed at least 99% of albumin-bound radioactive fatty acids under optimal conditions, whereas the amount of protein adsorbed onto charcoal was 4.9%. The protein that remained in solution following separation of the charcoal appeared to be native, as judged by a number of criteria, including analytical ultracentrifugation, optical rotatory dispersion, the ability to bind fatty acids, and the ability to bind the fluorescent dye, 8-anilinonaphthalene-1-sulfonic acid, as well as several other fluorescence parameters. Fluorescence spectra of human serum albumin samples indicated that impurities are sometimes present which can be removed by charcoal at neutral pH. A possible explanation for the gentleness of charcoal treatment is offered. Acid-charcoal treatment is a much more rapid method of removing lipid impurities than other methods previously described.

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

Abstract: Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.

Crystal structure of human serum albumin at 2.5 A resolution.

Abstract: A new triclinic crystal form of human serum albumin (HSA), derived either from pool plasma (pHSA) or from a Pichia pastoris expression system (rHSA), was obtained from polyethylene glycol 4000 solution. Three-dimensional structures of pHSA and rHSA were determined at 2.5 A resolution from the new triclinic crystal form by molecular replacement, using atomic coordinates derived from a multiple isomorphous replacement work with a known tetragonal crystal form. The structures of pHSA and rHSA are virtually identical, with an r.m. s. deviation of 0.24 A for all Calpha atoms. The two HSA molecules involved in the asymmetric unit are related by a strict local twofold symmetry such that the Calpha atoms of the two molecules can be superimposed with an r.m.s. deviation of 0.28 A in pHSA. Cys34 is the only cysteine with a free sulfhydryl group which does not participate in a disulfide linkage with any external ligand. Domains II and III both have a pocket formed mostly of hydrophobic and positively charged residues and in which a very wide range of compounds may be accommodated. Three tentative binding sites for long-chain fatty acids, each with different surroundings, are located at the surface of each domain.

The characterization of two specific drug binding sites on human serum albumin.

Abstract: The binding of a number of fluorescent probe molecules to human serum albumin (HSA) has been studied. Small changes in the amino acid moiety of the dansylamino acids resulted in large changes in the binding of these compounds to HSA. It is suggested that electrostatic and dipolar forces play a role in the specificity and binding affinity of such compounds. Fluorescent probes which had one tight binding site were used for drug displacement studies. Changes in probe fluorescence were shown, by equilibrium dialysis and by fluorescence titrations, to be a result of competitive displacement by drugs. The pattern of displacement of probes by drugs enabled the identification of two specific drug binding sites. The relative affinity of drugs for these binding sites was measured by their ability to displace fluorescent probes specific for the sites. The method provides a rapid and simple means for detecting potential drug interactions based on competition for protein binding sites.