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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To discover the antigenicity-producing mechanism of acetylsalicylic acid, the interaction of this drug and relevant salicylic acid with human serum albumin (HSA) has been studied by means of nuclear magnetic resonance (NMR) spectroscopy. The determination of spin-lattice relaxation rates (1/T1) of some protons have revealed that one HSA molecule can bind acetylsalicylate and salicylate up to 80 and 290 molecules, respectively. The hydrolysis rates of acetylsalicylate were greatly enhanced in the presence of HSA, especially when the drug/HSA mole ratio was small. Thus, the esterase-like activity of HSA was verified. This activity of HSA was effectively inhibited by salicylate; the effect was ascribed to the stronger binding affinity of salicylate toward HSA as compared with that of acetylsalicylate. Based on these results, the antigenicity-producing mechanism of acetylsalicylate and salicylate has been discussed.
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PMID:Acetylsalicylate-human serum albumin interaction as studied by NMR spectroscopy--antigenicity-producing mechanism of acetylsalicylic acid. 201 Nov 21

Testosterone-3-O-carboxymethyl-oxime derivative was synthetized and coupled to bovine serum albumin (BSA). The T-3-CMO-BSA conjugate homogenized with Freund's adjuvant used as immunogen was injected multiple sites in rabbits. The antisera collected were characterized in a radioimmunological system, separation with dextran-charcoal using 125I-Testosterone as tracer. The antibody titres varied from one animal to another. The titre of anti-T serum selected for RIA was 1: 10(4)-1: 2 X 10(4) (initial dilution). All anti-T sera 100 percent crossreacted with 5 alpha-dihydrotestosterone but nonsignificant interference was observed with other C19, C21 and C18 steroids. The affinity constant of the selected anti-T serum was in the range 1.4-1.9 X 10(9) litres/mole. The data so far published on the antisera toward testosterone are reviewed. We conclude that the selected anti-T-3-CMO-BSA serum may provide assays for testosterone with potential for clinical applications.
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PMID:The development of a radioimmunoassay system for testosterone (T) and dihydrotestosterone (DHT). Part 2. The preparation of antisera to T. 210 70

CTP:phosphocholine cytidylyltransferase present in rat liver cytosol was activated almost 30-fold when assayed in the presence of liposomes containing 60 mole % dioleoyl phosphatidylethanolamine (DOPE). During the assay, some of the DOPE was degraded to lysoPE and oleic acid. Whereas cytidylyltransferase activity was not affected when assayed in the presence of liposomes containing lysoPE, liposomes containing oleic acid activated the enzyme. Activation by oleic acid could be eliminated by the addition of fatty acid-free bovine serum albumin (BSA) to the assay. When cytidylyltransferase activity was measured in the presence of both BSA and liposomes containing DOPE, enzyme activity was increased almost 20-fold, as compared with assays performed in the absence of added lipid. The 1.5-fold difference in cytidylyltransferase activity observed when cytosol was assayed with DOPE containing liposomes in the absence or presence of BSA (30-fold stimulation vs 20-fold stimulation) cannot be explained by the loss of activation attributable to oleic acid alone. Activation of the enzyme in the presence of liposomes containing DOPE and oleic acid is several-fold greater than the sum of the activations caused by the individual compounds. These data suggest that PE and oleic acid act synergistically in activating the cytidylyltransferase.
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PMID:Synergistic activation of CTP:phosphocholine cytidylyltransferase by phosphatidylethanolamine and oleic acid. 215 9

Methotrexate (MTX) conjugate of a neoglycoprotein, mannosyl bovine serum albumin, containing an average of 30 moles of MTX per mole of neoglycoprotein was taken up efficiently by murine peritoneal macrophages through cell surface mannosyl receptors. The conjugate strongly inhibits the growth of Leishmania donovani inside macrophages, with 50% inhibitory dose of 0.11 micrograms/ml MTX, which makes it 100 times more active than free MTX (50% inhibitory dose of 12.1 micrograms/ml). MTX conjugated to BSA or other non-specific neoglycoproteins like galactose-BSA and glucose-BSA have leishmanicidal effects comparable to free MTX. Moreover, in a murine model of experimental visceral leishmaniasis, the drug conjugate reduced the spleen parasite burden by more than 85% in a 30 day model whereas the same concentration of free drug caused little effect. The results demonstrate that neoglycoproteins may be useful as carriers for receptor mediated drug delivery to treat macrophage associated diseases.
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PMID:Sugar receptor mediated drug delivery to macrophages in the therapy of experimental visceral leishmaniasis. 230 13

Bovine serum albumin (BSA) is routinely utilized in vitro to prevent the adverse detergent effects of long-chain acyl-CoA esters (i.e., palmitoyl-CoA) in enzyme assays. Determination of substrate saturation kinetics in the presence of albumin would only be valid if the relationship between bound and free substrate concentrations was known. To elucidate the relationship between bound and free palmitoyl-CoA concentrations in the presence of BSA, several different techniques including equilibrium dialysis, equilibrium partitioning, fluorescence polarization and direct fluorescence enhancement were investigated. Direct fluorescence enhancement using a custom synthesized fluorescent probe, 16-(9-anthroyloxy)palmitoyl-CoA (AP-CoA), was the best approach to this question. Measurement of the relationship between mol of palmitoyl-CoA bound per mol of BSA (nu) versus -log[free palmitoyl-CoA] revealed that the binding of palmitoyl-CoA to BSA, like palmitate was nonlinear, suggesting the presence of more than one class of acyl-CoA binding sites. Computer analyses of the binding data gave a best fit to the 2,4 two-class Scatchard model, suggesting the presence of two high-affinity primary binding sites (k1 = (1.55 +/- 0.46) x 10(-6) M-1) and four lower affinity secondary binding sites (k2 = (1.90 +/- 0.09) x 10(-8) M-1). Further analyses using the six parameter stoichiometric (stepwise) ligand binding model supports the existence of six binding sites with the higher affinities associated with the binding of the first mole of palmitoyl-CoA and weaker binding occurring after the first two sites are occupied. The association constants from this model of multiple binding diminish sequentially (i.e., K1 greater than K2 greater than K3 greater than...greater than or equal to K6), suggesting that each mol of long-chain acyl-CoA binds to BSA with decreasing affinities.
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PMID:The binding of palmitoyl-CoA to bovine serum albumin. 236 1

The binding of histamine, 4-methylhistamine (a histamine type 2 receptor agonist), cimetidine (a histamine type 2 receptor antagonist), and telemethylhistamine (an inactive analog) to human peripheral blood mononuclear cell subsets was investigated by flow cytometry by using conjugates of these ligands coupled to fluorescein-labeled human serum albumin. Our results indicate that binding of fluorescent protein conjugates of histamine and its analogs does not selectively identify a lymphocyte subset(s) that mediates the immunomodulatory effects of histaminergic ligands. Conjugates with both low (2.5 to 2.8:1) and high (28 to 57:1) ligand to protein coupling ratios were used. No binding above background could be detected for the low mole ratio reagents. The high mole ratio reagents were bound by 95 to 99% of all lymphocytes when used at ligand concentrations of 50 microM or greater. At lower ligand concentrations, the number of lymphocytes exceeding a set fluorescence threshold was decreased, but fluorescence distributions remained unimodal at all concentrations used (1 to 500 microM). Monocytes also bound the high mole ratio reagents and gave rise to a second high-intensity peak in the fluorescence distribution unless they were excluded by other means. Levels of conjugate binding detected by flow cytometry did not parallel ligand potencies at classical histamine type 2 receptors; at equivalent ligand concentrations, approximately equal amounts of histamine or 4-methylhistamine conjugate were bound per lymphocyte, and only 30% less telemethylhistamine conjugate was bound. Competition with free ligands (10(2)- to 10(4)-fold excess histamine, 4-methylhistamine, cimetidine, or telemethylhistamine) did not significantly decrease the level of binding observed for the high mole ratio reagents at bound ligand concentrations of 1 to 25 microM. Dual staining with fluorescein-labeled conjugate and phycoerythrin-labeled monoclonal antibodies Leu-3ab (anti-helper T), Leu-2a (anti-suppressor T), Leu-M3 (anti-monocyte), or anti-HLA-DR (B cells and monocytes) was also carried out. The extent of conjugate binding to helper and suppressor cells was identical for each of the ligands used, but higher levels of conjugate binding were seen for monocytes and B cells than for T cells in every case. Our data do not exclude the possibility of enhanced conjugate binding to small numbers of activated (HLA-DR positive) T cells that might be involved in mediation of histamine effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Binding of histamine and histamine analogs to lymphocyte subsets analyzed by flow cytometry. 241

Interaction of rat liver histone H1 fraction with the 5'-end of the rat serum albumin gene was localized within a 346 base pair (bp) restriction fragment. Sequence analysis of the fragment showed the fragment was 72 mol % adenosine-thymidine, which is significantly greater than the mole percent adenosine-thymidine composition of the rat genome. Gel retardation assays of the histone H1-DNA interaction indicate the complex formed behaves as previously characterized H1-DNA and shows a high-affinity H1 binding site within the enriched albumin restriction site. Deoxyribonuclease I (DNase I) protection assays on the H1 binding site define three protected regions only on the template strand of the DNA fragment. The three sites lie 55 and 110 bp apart (165 bp between the first and third binding site) with a consensus binding sequence of 5'-GA-ATA-CTGGCTT-C-TT-CTA-G-3'. The sequences between the protected DNA regions are highly enriched in adenosine-thymidine bases (79.3 and 86 mol % adenosine-thymidine, respectively). The functional significance is not understood.
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PMID:High-resolution analysis of a histone H1 binding site in a rat albumin gene. 245 58

A heterobifunctional linking reagent containing a masked aldehydo group and acyl hydrazide was synthesized for coupling of glycopeptides and other amino-containing compounds to proteins. After conversion to acyl azide, the reagent reacts with the amino group of a glycopeptide, and the modified glycopeptide is deacetalized with a weak acid to unmask the aldehydo group, which is then conjugated to bovine serum albumin (BSA) by reductive alkylation with pyridine-borane. The overall reaction scheme proceeds under relatively mild conditions. When the protein amino group was in a large excess (greater than 6-fold) of the aldehyde reagent, the efficiency of conjugation was as high as 88% even at submicromole levels. As a test case for application of this reagent, 6-aminohexyl beta-D-galactopyranoside (Gal-AH) was attached to the linking reagent and conjugated to BSA at various aldehyde-to-protein molar ratios ranging from 25 to 200. The level of O-galactosyl residue incorporated into BSA by this reagent far exceeded that observed in a similar reductive alkylation involving S-galactoside reagents [Lee, R. T., & Lee, Y. C. (1980) Biochemistry 19, 156-163]. By use of the present conjugating procedure, as many as 112 mol of Gal-AH residues were incorporated per mole of BSA, which represents near total modification of the amino groups. Some binding characteristics of the new BSA derivatives were studied in the mammalian hepatic galactose/N-acetylgalactosamine specific lectin system along with other types of BSA derivatives (containing S-galactosyl residues). In general, the behavior of the new derivatives was similar to that of other types. For instance, the affinity increased exponentially at low sugar substitution levels (up to 30 mol of galactosyl residues/mol of BSA), and the slope of exponential increase and affinity at a given sugar substitution level was similar to those of other types.
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PMID:Efficient coupling of glycopeptides to proteins with a heterobifunctional reagent. 247 Apr 4

The inhibition of dansylsarcosine (DS) binding at the benzodiazepine binding site of human serum albumin has been studied in the presence of saturated and unsaturated free fatty acids (FFA) of various chain lengths (C6-C20, C18:1, C18:2). In order to determine the mechanism of displacement, velocity constants for association (k2) and dissociation (k-2) and binding constants (KA and KA') have been measured using the stopped-flow method. The inhibitory effect of FFA on DS binding kinetics at site II is dependent of their structure. With increasing amounts of FFA the association velocity constant of DS binding decreases from 520 s-1 (fatty acid free albumin) by a factor of 3-10 and affinity decreases according to FFA chain length. Inhibition is strongest in the presence of caprylic, capric and lauric acid (C8-C12) i.e. with more than one mole FFA per mole albumin, DS association could no longer be measured. Short chain caproic and the long chain FFA C14-C20 showed only a less inhibitory effect since in the presence of a twofold excess k2 ranged between 100 and 200 s-1. Dissociation velocity of DS from the benzodiazepine binding site could be measured in relationship to FFA chain length using ibuprofene, another drug binding at site II. Dissociation velocity constants k-2 remained constant up to 2 moles FFA per mole albumin (k-2 = 16-18 s-1). A rise in k-2 to 70 s(-1) was seen, however, when 2-4 moles capric, lauric, myristic and palmitic (C10-C16) acid were bound, whereas no change was observed when increasing concentrations of caproic, caprylic, stearic and arachic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of drug binding to human serum albumin: allosteric and competitive inhibition at the benzodiazepine binding site by free fatty acids of various chain lengths. 247 Oct 88

Interaction of bilirubin with bovine serum albumin and its five succinylated forms was studied using fluorescence spectroscopy at two different ionic strengths i.e., 0.15 and 1.0 respectively. Affinity constant was found to be 1.8 x 10(7) litres/mole at 0.15 ionic strength which decreased to 4.4 x 10(6) litres/mole after 87% succinylation. On increasing ionic strength to 1.0, there was a slight decrease in affinity constant for native albumin. However, affinity constant remained same in 55 and 87% modified albumins at high ionic strength. These results suggest noninvolvement of surface lysine residues in bilirubin albumin complex.
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PMID:Noninvolvement of surface lysine residues of bovine serum albumin in bilirubin binding. 250 61


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