Human serum albumin

About: Human serum albumin is a research topic. Over the lifetime, 9402 publications have been published within this topic receiving 269029 citations. The topic is also known as: serum albumin & ALB.

Direct evidence for the formation of diastereoisomeric benzylpenicilloyl haptens from benzylpenicillin and benzylpenicillenic acid in patients

Abstract: Covalent binding to proteins to form neoantigens is thought to be central to the pathogenesis of penicillin hypersensitivity reactions. We have undertaken detailed mass spectrometric studies to define the mechanism and protein chemistry of hapten formation from benzylpenicillin (BP) and its rearrangement product, benzylpenicillenic acid (PA). Mass spectrometric analysis of human serum albumin exposed to BP and PA in vitro revealed that at low concentrations (drug protein molar ratio 0.001:1) and during short time incubations BP and PA selectively target different residues, Lys199 and Lys525, respectively. Molecular modeling showed that the selectivity was a function of noncovalent interaction before covalent modification. With increased exposure to higher concentrations of BP and PA, multiple epitopes were detected on albumin, demonstrating that the multiplicity of hapten formation is a function of time and concentration. More importantly, we have demonstrated direct evidence that PA is a hapten accounting for the diastereoisomeric BP antigen formation in albumin isolated from the blood of patients receiving penicillin. Furthermore, PA was found to be more potent than BP with respect to stimulation of T cells from patients with penicillin hypersensitivity, illustrating the functional relevance of diastereoisomeric hapten formation.

Optical Studies of Drug-Protein Complexes: II. Interaction of Phenylbutazone and Its Analogues with Human Serum Albumin

Abstract: The binding of phenylbutazone to human serum albumin generated a positive ellipticity band at 287 mµ in the circular dichroic spectrum of time protein. This extrinsic Cotton effect resulted from perturbation of the carbonyl chromophore of phenylbutazone by an asymmetrical locus at the albumin binding site. Hydrophobic interactions appeared to be important for the maintenance of a rigid drug-protein complex, since the introduction of hydrophilic groups into phenylbutazone caused considerable reduction in the magnitude of induced optical activity. Phenylbutazone competitively displaced 1-dimethylamino-naphthalene-5-sulfonyl-N-glycine (a fluorescent probe for the hydrophobic regions of proteins) from human serum albumin. This suggested that there was a hydrophobic area at or near one of the phenylbutazone-binding sites. The red shift in the ultraviolet absorption maximum of phenylbutazone on binding to albumin provided some evidence that the phenyl groups of the drug were located in a region of the protein where the dielectric constant was less than that of water.

Effects of Fatty Acids on Two Specific Drug Binding Sites on Human Serum Albumin

Abstract: Two distinct binding sites, I and II, for anionic drugs on human serum albumin have previously been demonstrated using fluorescent probe techniques. 5-Dimethylaminonaphthalene-1-sulfonamide (DNSA) and dansylsarcosine are specific fluorescent probes for sites I and II, respectively. The addition of fatty acids results in differing effects at the two binding sites, and the specificity of site II is lost. The order of potency of various fatty acids in causing these changes is oleic > stearic > linoleic [unknown] palmitic, and this is the same as the order of association constants for these fatty acids. It is concluded that chain length and degree of unsaturation determine both binding affinity and the extent to which the fatty acids induce configurational adaptations in the albumin molecule. Furthermore, studies with varying ratios of oleic acid to albumin suggest that the conformational changes induced in the protein are different for each molecule of oleic acid added. Addition of oleic acid at a 3:1 molar ratio with albumin significantly increased the binding of warfarin and DNSA to site I.

Re-formation of the Helical Structure of Human Serum Albumin by the Addition of Small Amounts of Sodium Dodecyl Sulfate after the Disruption of the Structure by Urea. A Comparison with Bovine Serum Albumin

Abstract: Upon the addition of small amounts of sodium dodecyl sulfate (SDS), the helicity of human serum albumin (HSA), lost in the urea denaturation, was mostly recovered. The profile of the recovery differed depending on the urea concentration. Then the urea concentrations were divided into three ranges: [1] a range below 3 M where the helicity only decreased as in the absence of urea (the helicity decreased down to 49% in the SDS solution); [2] a range between 4 and 8 M where the helicity initially increased up to 66% (this was the same as in the native state) and then sharply decreased; [3] a range above 9 M where the helicity only increased with an increase in added SDS concentration. When SDS was added prior to the urea denaturation, the same helicity was obtained at each surfactant concentration. Thus the SDS denaturation finally predominates over the urea denaturation. In the middle range, profiles of the structural change were rather complicated. The increase and decrease of helicity were accomplished be...