Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated plasma protein binding by the novel oral hypoglycemic agent, repaglinide, and assessed the influence of other protein-bound drugs upon this process. Varying concentrations of [3H]-repaglinide (0.01 to 100 micrograms/ml) were incubated in solutions of plasma proteins (human serum albumin, HSA; alpha 1-acid glycoprotein, AAGP), or human plasma in the absence or presence of several test drugs. Protein binding was assessed using an ultrafiltration technique. At all concentrations tested, the mean binding of repaglinide in plasma was 98.5%, binding to HSA averaged 98.6%, and the binding to AAGP was saturable and remained below 50%. Warfarin 10 micrograms/ml, furosemide 0.2 microgram/ml, and tolbutamide 100 micrograms/ml, significantly reduced in vitro binding of repaglinide at 1 and 100 micrograms/ml versus control (p < 0.05), producing an 18-36% increase in free repaglinide. No reduction was found using 0.1 microgram/ml repaglinide. Diazepam, glibenclamide and nicardipine hydrochloride had no significant effects on the in vitro protein binding of repaglinide. These data suggest that the binding of repaglinide to HSA in human plasma has potential clinical significance, and that within the therapeutic range for repaglinide, the presence of the test drugs has no clinically relevant effects on repaglinide binding to plasma proteins.
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PMID:The effects of selected drugs on the in vitro protein binding of repaglinide in human plasma. 1089 94

Cosalane is a potent inhibitor of HIV replication with multiple sites of action. The purposes of this study were to (a) determine the extent and nature of cosalane binding to mucin, alpha(1)-acid glycoprotein (AAG), plasma, and human (HSA) and bovine serum (BSA) albumin, and (b) determine the primary site(s) of cosalane binding to HSA. Plasma protein binding of cosalane was studied by a gel filtration technique. Cosalane binding to HSA was also determined in the presence of salicylic acid. Competitive inhibition studies were conducted using warfarin, digitoxin, and diazepam to determine the primary HSA binding site(s) of cosalane. The drug was bound extensively to HSA and BSA and required 500-550 moles to saturate 1 mole of protein. Stoichiometries of cosalane binding to alpha(1)-acid glycoprotein (AAG) and mucin were between 30 and 50 mol/mol of either glycoprotein. The binding isotherm deviated from a rectangular hyperbola, suggesting self-association of the ligand. Salicylic acid decreased cosalane binding to HSA by one order of magnitude. Inhibition studies of cosalane to HSA revealed that the compound binds primarily to warfarin site with a K(i) of 1.24 +/- 0.24 nM. In summary, cosalane binds extensively to serum albumins and to a lesser extent to both AAG and mucin.
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PMID:Binding of cosalane--a novel highly lipophilic anti-HIV agent--to albumin and glycoprotein. 1128 10

N-glycans of the mouse glycoprotein HSA and its human analogue CD24 from lymphoblastoma, neuroblastoma and astrocytoma cell lines as well as from mouse brain homogenate were analysed and compared to each other and to the N-glycosylation pattern of total glycoproteins from mouse and human brain. The N-glycans were released from PVDF-blotted HSA or CD24 and separated on Carbograph SPE into neutral and acid glycans. The naturally neutral glycan fraction and the fraction of glycans rendered neutral after neuraminidase treatment were analysed without further purification by MALDI-MS. In each fraction, about 25 molecular ions with an intensity >10% of the base peak were identified which corresponded to glycans with distinct isobaric monosaccharide compositions. Comparison of the neutral and desialylated glycans revealed some similarities between the samples analysed, but also clear differences. HSA and CD24 from all cell lines express almost no neutral N-glycans with two or more fucose in contrast to brain HSA and glycoproteins from mouse and human brain. The lack of extensive fucosylation was also observed for desialylated glycans of HSA and CD24 from all cell lines analysed except for CD24 from a human neuroblastoma cell line which exhibits like total human and mouse brain glycoproteins a large variety of highly fucosylated, higher branched N-glycans. HSA from mouse brain carries in addition desialylated non-fucosylated glycans of high abundance which were detected, if at all, only at low intensity in all other samples analysed suggesting that they may be implicated in specific functions of mouse brain HSA. Therefore, a rapid assessment of similarities or differences between glycosylation patterns of a glycoprotein isolated from different sources is possible using methods as described here.
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PMID:N-glycosylation patterns of HSA/CD24 from different cell lines and brain homogenates: a comparison. 1282 73

Human alpha(1)-acid glycoprotein (AGP) or orosomucoid (ORM) is a major acute phase protein that is thought to play a crucial role in maintaining homeostasis. Human AGP is the product of a cluster of at least two adjacent genes located on HSA chromosome 9. Using a range of restriction endonucleases we have investigated DNA variation at the locus encoding the AGP genes in a group of healthy Caucasians. Polymorphisms were identified using BamHI, EcoRI, BglII, PvuII, HindIII, TaqI and MspI. Nonrandom associations were found between the BamHI, EcoRI and BglII RFLPs. The RFLPs detected with PvuII, TaqI and MspI were all located in exon 6 of both AGP genes. The duplication of an AGP gene was observed in 11% of the individuals studied and was in linkage disequilibrium with the TaqI RFLP. The identification and characterization of these polymorphisms should prove useful for other population and forensic studies.
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PMID:Identification and characterization of polymorphisms at the HAS alpha1-acid glycoprotein (ORM*) gene locus in Caucasians. 1496 18

A dithiolated random copolymer with pendent phenylboronic acid residues [Cys-poly(3-acrylamidophenylboronic acid-co-N,N-dimethylaminopropyl methacrylamide), Cys-poly(APBA-co-DMAPMA)] that shows the abilities of initiation, transfer, and termination (iniferter) was obtained by using a benzyl N,N-diethyldithiocarbamoyl (BDC) derivative. The obtained disulfide-carrying copolymer was accumulated on a colloidal gold-immobilized glass substrate, and the usefulness of the polymer brush as a sensing element for glycoproteins such as ovalbumin (OVA) was examined by UV-visible spectrophotometry with the help of localized surface plasmon resonance (LSPR). The sensor showed a concentration-dependent binding of OVA with a detection limit of 100 nM, and it had a very high stability at high ionic strength. The sensor chip could be used for a detection of another glycoprotein, avidin, as well. Furthermore, the binding of biotin-modified human serum albumin (biotinylated HSA) to the avidin-phenylboronic acid- (PBA-) carrying polymer brush complex and further specific binding of anti-HSA immunoglobulin G to the biotinylated HSA-avidin-PBA-carrying polymer brush ternary complex could clearly be observed. The polymer-brush-coated device examined here not only was useful as a simple sensor chip, but also is expected to open a new perspective on interfacial phenomena performed by various functional polymer brushes fixed to colloidal gold on glass substrates.
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PMID:Sensing capabilities of colloidal gold monolayer modified with a phenylboronic acid-carrying polymer brush. 1660 22

Drug-protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; alpha(1)-acid glycoprotein (AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, beta-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-frontal analysis is presented. Furthermore, the binding of these drugs to all plasmatic proteins is evaluated by using ultrafiltration and CE. The results indicate that the hydrophobic character of compounds seems to be the key factor on the interaction between cationic drugs towards proteins. In fact, hydrophobic basic drugs bind in great extension to HSA, while hydrophilic basic drugs present low interactions with proteins and bind especially to AGP.
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PMID:Characterization of basic drug-human serum protein interactions by capillary electrophoresis. 1694 56

The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with alpha(1)-acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants of drug enantiomers to HSA and the evaluation of the binding sites of antihistamines on the HSA molecule. The developed methodology includes the ultrafiltration of samples containing HSA and racemic antihistaminic drugs and the analysis of the free or bound drug fraction using the affinity EKC-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of antihistamines to HSA, the major plasmatic protein.
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PMID:Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE. 1760 50

Human plasma protein binding of six antimalarial agents of quinoline and acridine types was investigated by using spectroscopic techniques, affinity chromatography, ultrafiltration and HPLC methods. Induced circular dichroism (ICD) spectra showed binding of amodiaquine (AMQ), primaquine (PRQ), tafenoquine (TFQ), and quinacrine (QR) to alpha(1)-acid glycoprotein (AAG), the serum level of which greatly increases in Plasmodium infections. Association constant (K(a)) values of about 10(5)-10(6) M(-1) could be determined. Analysis of the ICD and UV spectra of the drug-AAG complexes suggested the inclusion of the ligands into the central hydrophobic cavity of the protein. Using the purified forms of the two main genetic variants of AAG, ICD data indicated the selective binding of AMQ and PRQ to the 'F1/S', while QR to the 'A' variant. Results of fluorescence experiments supported the AAG binding of these drugs and provided further insights into the binding details of TFQ and QR. Fluorescence and CD displacement experiments showed the high-affinity AAG binding of mefloquine (K(a) approximately 10(6) M(-1)). For this drug, inverse binding stereoselectivities were found with the 'F1/S' and 'A' genetic variants of AAG. HSA association constants estimated from affinity chromatography results lag behind (10(3)-10(5) M(-1)) the similar values derived for AAG. In case of chloroquine, no significant binding interaction was found either with AAG or HSA. Pharmacological aspects of the results are discussed.
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PMID:Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein. 1828 58

Sialyl Lewis(a) (sLe(a)), also termed CA19-9 antigen, is recognized by murine mAb19-9 and is expressed on the cancer cell surface as a glycolipid and as an O-linked glycoprotein. It is highly expressed in a variety of gastrointestinal epithelial malignancies including colon cancer and pancreatic cancer, and in breast cancer and small cell lung cancer, but has a limited expression on normal tissues. sLe(a) is known to be the ligand for endothelial cell selectins suggesting a role for sLe(a) in cancer metastases and adhesion. For these reasons, sLe(a) may be a good target for antibody mediated immunotherapy including monoclonal antibodies and tumor vaccines. However, sLe(a) is structurally similar to sLe(x) and other blood group related carbohydrates which are widely expressed on polymorphonucleocytes and other circulating cells, raising concern that immunization against sLe(a) will induce antibodies reactive with these more widely expressed autoantigens. We have shown previously both in mice and in patients that conjugation of a variety of carbohydrate cancer antigen to keyhole limpet hemocyanin (KLH) and administration of this conjugate mixed with saponin adjuvants QS-21 or GPI-0100 are the most effective methods for induction of antibodies against these cancer antigens. We describe here for the first time the total synthesis of pentenyl glycoside of sLe(a) hexasaccharide and its conjugation to KLH to construct a sLe(a)-KLH conjugate. Groups of five mice were vaccinated subcutaneously four times over 6 weeks. Sera were tested against sLe(a)-HSA by ELISA and against sLe(a) positive human cell lines adenocarcinoma SW626 and small cell lung cancer (SCLC) DMS79 by FACS. As expected, mice immunized with unconjugated sLe(a) plus GPI-0100 or unconjugated sLe(a) mixed with KLH plus GPI-0100 failed to produce antibodies against sLe(a). However, mice immunized with sLe(a)-KLH conjugate without GPI-0100 produced low levels of antibodies and mice immunized with sLe(a)-KLH plus GPI-0100 produced significantly higher titer IgG and IgM antibodies against sLe(a) by ELISA. These antibodies were highly reactive by FACS and mediated potent complement mediated cytotoxicity against sLe(a) positive SW626 and DMS79 cells. They showed no detectable cross reactivity against a series of other blood group-related antigens, including Le(y), Le(x), and sLe(x) by dot blot immune staining. This vaccine is ready for testing as an active immunotherapy for treating sLe(a) positive cancer in clinical settings.
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PMID:Synthesis of sialyl Lewis(a) (sLe (a), CA19-9) and construction of an immunogenic sLe(a) vaccine. 1919 Sep 7

The binding of drugs with proteins in blood, serum, or plasma is an important process in determining the activity, distribution, rate of excretion, and toxicity of drugs in the body. High-performance affinity chromatography (HPAC) has received a great deal of interest as a means for studying these interactions. This review examines the various techniques that have been used in HPAC to examine drug-protein binding and discusses the types of information that can be obtained through this approach. A comparison of these techniques with traditional methods for binding studies (e.g., equilibrium dialysis and ultrafiltration) will also be presented. The use of HPAC with specific serum proteins and binding agents will then be discussed, including HSA and alpha(1)-acid glycoprotein (AGP). Several examples from the literature are provided to illustrate the applications of such research. Recent developments in this field are also described, such as the use of improved immobilization techniques, new data analysis methods, techniques for working directly with complex biological samples, and work with immobilized lipoproteins. The relative advantages and limitations of the methods that are described will be considered and the possible use of these techniques in the high-throughput screening or characterization of drug-protein binding will be discussed.
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PMID:Characterization of drug-protein interactions in blood using high-performance affinity chromatography. 1927 6


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