Showing papers on "Human serum albumin published in 1992"
TL;DR: The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 Å and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serumalbumin.
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.
3,482 citations
Journal Article•
TL;DR: If pH, PCO2, and the concentrations of serum albumin and phosphate are measured, all independent variables, which physically determine "acid-base balance" in plasma, can be quantified and new ways to evaluate "unidentified anions" in metabolic acidosis can be explored.
353 citations
TL;DR: As deduced from whole-body autoradiography and quantitative distribution experiments, the 14C-labelled polymer is rapidly captured by liver, bone marrow, lymph nodes, spleen and peritoneal macrophages, by incorporation of 14C into endogenous compounds.
199 citations
TL;DR: In this article, a genetically engineered HSA-CD4 hybrid was designed to specifically block the entry of the human immunodeficiency virus into CD4+ cells, which is correctly processed and efficiently secreted by Kluyveromyces yeasts.
Abstract: Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+ cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.
194 citations
TL;DR: The enantioselective binding to HSA exhibited by warfarin, suprofen and ketoprofen was found to be due to differential binding of the enantiomers at Site I; the primary binding site for suprofe and ketofen was not enantiOSElective.
138 citations
TL;DR: Frontal analysis, using R-warfarin and L-tryptophan as probes for these sites, demonstrated that the immobilized HSA had binding behavior equivalent to that observed for HSA in solution, and thyroxine was binding directly to both types of site.
119 citations
TL;DR: Photon correlation spectroscopy and laser doppler anenometry showed that the coating reduced the adsorption of the protein to the polystyrene microspheres surface, which confirmed that the hydrophilic polyoxyethylene steric layer, created by coating with the block copolymers, reduced the advertisers of human serum albumin.
87 citations
Journal Article•
TL;DR: It is suggested that the nomenclature currently used to describe drug binding to human serum albumin may be misleading and it may be preferable to adopt the terms type I and type II binding, according to the displacement patterns of the compound concerned.
Abstract: The displacement of a series of 1,4-benzodiazepine (BDZ) drugs from a chiral stationary phase, based upon human serum albumin, for high performance liquid chromatography was investigated. The different displacement patterns obtained using various mobile phase additives could not be interpreted in terms of binding of the solutes to a single site. The observations were better described by considering the attachment of the BDZs to several loci on the protein. Two main mechanisms of binding were discerned, a nonstereoselective mode, which affected all solutes and seemed to occur at a large number of locations on the protein, and a highly stereoselective mode, which involved only one enantiomer of chiral BDZs and presumably one conformation of certain achiral solutes. The stereoselective binding mode encompassed at least four different sites, each of which displayed slightly different structural requirements. It is suggested that the nomenclature currently used to describe drug binding to human serum albumin may be misleading. Rather than the use of site I or site II, it may be preferable to adopt the terms type I and type II binding, according to the displacement patterns of the compound concerned. This approach would retain the conceptual simplicity of the current notation, while avoiding misleading implications of the exact molecular locus of binding.
80 citations
TL;DR: It is concluded that the disulfide-reduced state with partially folded variable conformation is involved in the reversible interconversion between the denatured reduced form and the native disulfides-bonded form of human serum albumin.
79 citations
Journal Article•
TL;DR: Good correlations were obtained between the receptor index and conventional liver function tests, such as the Child-Turcotte criteria score, and the plasma disappearance rate of indocyanine green, suggesting that the receptors index is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.
78 citations
TL;DR: In this article, denaturation temperatures and enthalpies of bovine serum albumin (BSA) and HSA measured by DSC at different pH values and protein concentrations are compared with the literature data on BSA, or SH-blocked BSA.
TL;DR: There is evidence that Diclofenac specifically blocks at least one of the major glycation sites of human serum albumin, which is probably responsible for the initiation of complications in diabetes patients and aging individuals.
TL;DR: In this paper, the authors compared the reactivity of VPA-G and VPAG-R towards covalent VPAprotein adduct formation by incubation in buffer, human serum albumin (HSA) and fresh human plasma at pH 7.4 and 37 degrees.
TL;DR: Reducing the disulfide bonds of HSA, and subsequent alkylation of the half-cystine residues, significantly decreased the affinity for protein G.
Abstract: Protein G is a streptococcal cell wall protein with separate and repetitively arranged binding domains for immunoglobulin G (IgG) and human serum albumin (HSA). In this work, the binding of protein G to HSA was studied. The results suggest that a single binding site is present on HSA: the apparent size of the HSA-protein G complex (230 kDa) corresponded to two or three HSA molecules bound to one protein G molecule, and Ouchterlony immunodiffusion did not yield any precipitate between protein G and HSA. HSA was cleaved by pepsin and CNBr into several fragments which were identified by SDS-PAGE and N-terminal amino acid sequencing, and the binding of protein G to the fragments was studied in Western blot experiments. The results indicated that the binding area was located in disulfide loops 6-8, involving both the second (loop 6) and the third (loops 7 and 8) domain of HSA. One of the protein G binding pepsin fragments, with an apparent molecular mass of 5.5 kDa, located in loops 7 and 8, was isolated and found to completely inhibit the binding between protein G and the intact HSA, again suggesting a single protein G binding site on serum albumin. Reducing the disulfide bonds of HSA, and subsequent alkylation of the half-cystine residues, significantly decreased the affinity for protein G. Protein G bound to albumin from baboon, cat, guinea pig, hamster, hen, horse, man, mouse, and rat, but not to albumin from cow, dog, goat, pig, rabbit, sheep, snake, or turkey.
TL;DR: Results of the reaction in the presence of excess N-CBZ-D(L)-AlaNP over HSA indicated the existence of one strong reactive site on HSA, and the effects of the reversible binding of the site-specific drug and the chemical modification by site- specific reagents on the HSA activity showed that the reactive site is the R site located near tyrosine-411 residue of HSA.
Abstract: The reactions of human serum albumin (HSA) with optically active amino acid p-nitrophenyl esters (substrate, S) were examined kinetically at 25°C. The rate data were analyzed in terms of a mechanism involving 1 : 1 complexing (S·HSA) between S and HSA. The dissociation constant (KS in M) and the catalytic rate constant (k2 in S-1) of S·HSA were determined. Among ten substrates examined, the reactions with N-carbobenzoxy-D(L)-alanine p-nitrophenyl esters (N-CBZ-D(L)-AlaNP) were most accelerated by HSA. Results of the reaction in the presence of excess N-CBZ-D(L)-AlaNP over HSA indicated the existence of one strong reactive site on HSA. The effects of the reversible binding of the site-specific drug and the chemical modification by site-specific reagents on the HSA activity showed that the reactive site towards N-CBZ-D(L)-AlaNP is the R site located near tyrosine-411 residue of HSA.
TL;DR: In this paper, the involvement of the cystinyl sulfur atoms in the ligation to the zinc group ions has been obtained from the X-ray photoelectron spectra, and it was inferred that these binding sites may be located at the seventeen disuifide bridges, most likely at the seven pairs of adjacent disulfide bridges between positions 75 and 567, in the serum albumins.
Patent•
14 Feb 1992TL;DR: In this paper, the authors used recombinant DNA techniques to produce polypeptides corresponding to mature human serum albumin residues 1 to n, where n is between 369 and 419 inclusive, which are useful as substitutes for albumin in the treatment of burns and shock in humans.
Abstract: Polypeptides corresponding to mature human serum albumin residues 1 to n, where n is between 369 and 419 inclusive, are useful as substitutes for albumin in the treatment of burns and shock in humans, the clearance of undesirable compounds, (such as bilirubin) from human blood, in laboratory growth media and in HSA assays. The polypeptides may be produced by recombinant DNA techniques, especially in yeast.
TL;DR: The isolation of a 48-kDa albumin-binding protein from a streptococcal strain (DG12) revealed a unique NH2-terminal sequence and three types of repeats in the encoded protein, and it was demonstrated that the albumin binding of the DG12 protein was localized within these domains.
Abstract: Many streptococcal strains are known to bind the two most abundant plasma proteins, namely, immunoglobulin G and albumin. Protein G isolated from group C and G streptococci has been demonstrated to have separate binding regions for each of these proteins. However, some group G streptococcal strains bind only serum albumin. This report describes the isolation of a 48-kDa albumin-binding protein from such a strain (DG12). The affinity constant of this protein for human serum albumin was determined to be 5 x 10(9) M-1, and the protein interacted strongly also with serum albumin from several other mammalian species. The gene encoding the albumin-binding protein was cloned and expressed in Escherichia coli. DNA sequence analysis of this gene revealed a unique NH2-terminal sequence and three types of repeats in the encoded protein. One of these repeated sequences has significant homology with the albumin-binding domains of protein G, and it was demonstrated that the albumin binding of the DG12 protein was localized within these domains. Another type of repeat is localized in the putative wall-spanning region of the molecule. This repeat sequence, which has the length of only 4 amino acids (LysProGluVal), is repeated 14 times. The relationship of the albumin-binding protein to other cell-wall-associated proteins of pathogenic streptococci is discussed.
TL;DR: It is proposed that albumin, rather than plasma esterases, catalysed the hydrolysis of ketoprofen glucuronides and the existence of separate binding and catalytic sites on the albumin molecule for these metabolites is proposed.
TL;DR: It is concluded that the uraemic binding defect of HSA is caused by competitive inhibition by the many physiological ligands accumulated in CRF and structural modifications of H SA.
Abstract: The binding capacity of human serum albumin (HSA) for small acidic molecules is known to be reduced in chronic renal failure (CRF). The contribution of competitive inhibition by accumulated endogenous ligands and of structural changes in HSA has now been evaluated. In a fluorimetric in vitro assay using HSA and two dansylated amino acids the inhibitory properties of various endogenous ligands were determined in concentration-effect studies. The effect of carbamylation of HSA on binding was also examined. The mode of inhibition, including binding parameters n and Ka, was determined. Finally, HSA binding in sera from controls and dialysis patients was compared in a modified assay.
TL;DR: The data indicate that Lys190 is the primary PLP binding site, which is distinct from other sites of covalent adduct formation; namely, the primary sites for nonenzymatic glycosylation and acetylation by aspirin (Lys199).
TL;DR: The data suggest that elevated plasma free tryptophan and the resulting altered serotonin metabolism seen in diabetes are independent of increased NEG and likely result from diabetic hyperlipidemia.
TL;DR: The binding of nine diazepines to human serum albumin and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies and the driving force for the binding appears to be hydrophobic interaction.
TL;DR: Since the quantum yields for photoisomerization and luminescence of bilirubin bound to serum albumin at room temperature are both low, internal conversion processes, rather than Z→E configurational isomerizations, are probably the major pathways for deactivation of photo‐excited bilirube.
Abstract: The quantum yield, phi ZE, for configurational photoisomerization (4Z,15Z----4Z,15E) of bilirubin bound non-covalently to human serum albumin was determined (at 23 +/- 2 degrees C) by laser excitation and chromatographic analysis of products. Values obtained for photoexcitation at 465 nm were about one-half those previously reported. The quantum yield was dependent on excitation wavelength, decreasing from a value of 0.109 +/- 0.010 for excitation at 457.9 nm to a value of 0.054 +/- 0.005 for excitation at 514.5 nm. The wavelength dependence is consistent with rapid transfer of excitation energy between the two non-identical pyrromethenone chromophores of bilirubin in the singlet excited state. Since the quantum yields for photoisomerization and luminescence of bilirubin bound to serum albumin at room temperature are both low, internal conversion processes, rather than Z----E configurational isomerizations, are probably the major pathways for deactivation of photo-excited bilirubin.
TL;DR: Two experiments were performed to assess the effect of supplemental protein source on sheep embryo development in vitro when incubated in synthetic oviduct fluid medium (SOF).
TL;DR: A study of the fluorescence quenching of human serum albumin by caffeine, theophylline and theobromine, based on temperature dependence, has shown that it is predominantly static.
TL;DR: The Lowry method is shown how it can be used for the determination of proteins immobilized on the surface of microspheres (for protein concentrations higher than 10 micrograms/ml).
Abstract: In this paper we show how the Lowry method, designed for the determination of proteins in solution, can be used for the determination of proteins immobilized on the surface of microspheres (for protein concentrations higher than 10 micrograms/ml). Measurements were made for human serum albumin (HSA) and for immunoglobulins [rabbit immunoglobulins--antibodies against human fibrinogen (IgGF) and against fragment D of human fibrinogen (IgGFgD)] immobilized on the surface of polystyrene microspheres.
TL;DR: The in situ modification of an immobilized human serum albumin (HSA) high-performance liquid chromatographic chiral stationary phase by p-nitrophenyl acetate is reported, suggesting that the affected binding area is not a single, tightly structurally defined site.
Abstract: The in situ modification of an immobilized human serum albumin (HSA) high-performance liquid chromatographic chiral stationary phase by p-nitrophenyl acetate is reported. This procedure, which is thought to affect primarily a single reactive tyrosine residue within the protein structure, influenced the chromatographic retention and enantioselectivity factors of a wide range of solutes. For certain solutes, increases in both capacity factor and chiral resolution were observed. Ultrafiltration studies on representative test solutes using free HSA, treated in a similar manner to the immobilized protein, gave similar results as the chromatographic observations, indicating that the latter effects are not artifactual results of immobilization. The effect of the modification of HSA on the binding behavior of drugs reportedly sharing the site predominantly affected by the derivatization, namely, the indole–benzodiazepine binding site, varied greatly. This observation suggests that the affected binding area is not a single, tightly structurally defined site.
TL;DR: Etoposide binding evaluated in single-source donor plasma was concentration-dependent over a concentration range of 1 to 250 micrograms/mL, and was significantly correlated with albumin concentration, suggesting that the single class of binding sites is on albumin.
TL;DR: These novel liquid affinity supports present an exciting opportunity to develop a range of unit operations for the continuous purification of proteins.