Abstract：
:Cyclophilin (163 amino acids; 17,737 daltons) is a ubiquitous cytosolic protein that specifically binds the potent immunosuppressive drug cyclosporin A (CsA). To characterize the structural details of this interaction, extensive use has been made of two-dimensional (2D) NMR methods. For studies on CsA, these methods are being used to assign the conformational space accessible to CsA by analysis of the spectra from the multiple CsA conformers present in slow exchange in mixed solvent systems. These same 2D NMR methods also have been used for extensive studies of the major bovine thymus cyclophilin (CyP) isoform and its complex with stoichiometric amounts of CsA. In the former case, these studies have revealed 81% of the 156 expected HN-H alpha crosspeaks. The complete spin-coupled spin systems for one-third of these amide resonances have been assigned according to amino acid type. After exhaustive D2O exchange, there remain 44 amide protons which exhibit 2D NMR features indicative of a hydrophobic domain with beta-sheet secondary structure. The CsA-complexed form of CyP exhibits a discrete structure and set of resonances in slow exchange with the drug-free CyP. The amino acids that have been specifically identified to be affected by the interaction are limited in number and include three Phe residues, the unique Trp at position 120, and two Ala residues.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hsu VL,Heald SL,Harding MW,Handschumacher RE,Armitage IMdoi
10.1016/0006-2952(90)90188-qsubject
Has Abstractpub_date
1990-07-01 00:00:00pages
131-40issue
1eissn
0006-2952issn
1873-2968pii
0006-2952(90)90188-Qjournal_volume
40pub_type
杂志文章abstract：:The effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 and C activation in signal transduction system of rabbit platelet was studied. Isotetrandrine, cepharanthine and berbamine inhibited the aggregation induced by collagen but not by other stimuli such as thrombin and arachidonic acid, whil...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90539-h
更新日期：1991-02-01 00:00:00
abstract：:By means of Sephadex G-75 and CM-Sephadex C-50 column chromatography and reverse-phase HPLC, a low molecular weight (Mr = 7500), cysteine-rich peptide, halysin, was purified from Agkistrodon halys (mamushi) snake venom. Halysin is a potent platelet aggregation inhibitor that concentration-dependently inhibited human p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90256-5
更新日期：1991-08-22 00:00:00
abstract：:In the rat, the highly potent anti-herpes drug (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) is rapidly converted to its base (E)-5-(2-bromovinyl)uracil (BVUra) through the action of pyrimidine nucleoside phosphorylases. However, BVdUrd can be regenerated or even generated de novo from BVUra by a pentosyl transfer rea...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90318-7
更新日期：1986-05-15 00:00:00
abstract：:Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mecha...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90342-g
更新日期：1992-12-01 00:00:00
abstract：:Novel hydroxynaphthoquinones have been shown to be potent and selective inhibitors of mitochondrial electron transport in the protozoan Eimeria tenella, inhibiting at concentrations of 10(-10) to 10(-11)M. The primary site of electron transport inhibition has been localized to the ubiquinol-cytochrome c reductase span...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90581-1
更新日期：1984-07-01 00:00:00
abstract：:Exposures of cultured whole rat conceptuses during organogenesis to 3-methylcholanthrene (MC; 0.025-25 microM), 5,6-benzoflavone (BNF; 5-100 microM) or benz[a]anthracene (BA; 5-100 microM) were effected by placement of each of these "MC-type" inducing agents in the culture medium at the time of explantation on day 9.5...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90467-7
更新日期：1994-11-01 00:00:00
abstract：:Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspirat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00074-9
更新日期：1997-05-09 00:00:00
abstract：:The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack of target validation in human subjects. The dopamine transporter has historically been a primary target for cocaine abuse medication development, but ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2007.08.007
更新日期：2008-01-01 00:00:00
abstract：:The anti-anginal agent bepridil blocks slow Ca2+ channels in a variety of tissues. Since bepridil accumulates inside cells, the possibility exists that bepridil acts, at least partially, from inside the cell. To test this possibility, we examined the effects of a quaternary ammonium analog of bepridil, methylated bepr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90460-0
更新日期：1986-07-15 00:00:00
abstract：:Low-density lipoprotein (LDL) has been proposed as carrier for the selective delivery of anticancer drugs to tumor cells. We reported earlier the association of several lipidic steroid-conjugated anticancer oligodeoxynucleotides (ODNs) with LDL. In the present study, we determined the stability of these complexes. Whe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00243-4
更新日期：2000-06-01 00:00:00
abstract：:Doxorubicin is shown to be present in albumin microspheres (10-40 microns) in two forms: the native drug and a fraction of drug covalently coupled to the protein matrix probably via glutaraldehyde. Upon trypsin digestion the fraction covalently coupled is released and can be resolved from native doxorubicin by high pe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90123-m
更新日期：1991-06-15 00:00:00
abstract：:Homogenization of rat kidney under isotonic conditions and in the presence of protease inhibitors showed that some 92% of the cyclic AMP phosphodiesterase activity and some 83% of the cyclic GMP phosphodiesterase activity was released into the soluble fraction. Analysis of soluble phosphodiesterase activity by FPLC on...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90678-e
更新日期：1990-07-15 00:00:00
abstract：:Accumulation of radioactive iron (59Fe) into isolated fragments of rat small intestine in the presence of two hydroxypyrones, maltol and ethyl maltol, was compared with that in the presence of another chelator of iron(III), nitrilotriacetic acid (NTA). The characteristics of uptake were similar with all three ligands....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90556-4
更新日期：1988-05-15 00:00:00
abstract：:Administration of phenobarbital to chick embryos increased hepatic microsomal UDP-glucuroyltransferase activity some 25-fold. The large phenobarbital-induced increase of UDP-glucuronyltransferase activity was correlated to an equivalent increase of immunochemically measurable UDP-glucuronyltransferase protein. Poly(A+...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90159-0
更新日期：1986-04-01 00:00:00
abstract：:The subcellular localization of a binding site for the competitive thromboxane A2/prostaglandin H2 (TXA2/PGH2) antagonist, 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4- hydroxyphenyl)-13,14-dihydro-13-aza-15 alpha beta-omega-tetranor TXA2 ([125I]-PTA-OH), was determined. Subcellular fractions of platelets were prep...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90138-4
更新日期：1988-02-15 00:00:00
abstract：:Purified red blood cell cytosol is able to activate 2-aminofluorene (2AF) to N-hydroxy-2-aminofluorene. Apparent kinetic parameters are determined with and without methylene blue. The latter, which maintains haemoglobin in the reduced form and stimulates NADPH production, increases the affinity of the enzyme for the 2...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90691-b
更新日期：1992-12-15 00:00:00
abstract：:The importance of polyglutamation for the activation of natural folates and classical antifolates and recent evidence for the role of dietary folate as a biochemical modulator of antifolate efficacy led us to investigate the influence of changes in dietary folate on folylpolyglutamate synthetase (FPGS) activity. Activ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00554-0
更新日期：1996-11-08 00:00:00
abstract：:The effect of naturally occurring aliphatic carboxylic acid n-butyrate on total and type-specific synthesis of sulfated proteoglycans and hyaluronic acid by rat liver fat-storing cells (Ito cells, vitamin A-storing cells), the main connective tissue producing cell type in liver, was studied. Concentrations of n-butyra...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90414-5
更新日期：1988-10-01 00:00:00
abstract：:The molecular mechanism(s) underlying induction of the hepatic microsomal cytochrome P4502E1 (2E1) by xenobiotics (e.g. ethanol and acetone) is controversial. Proposed mechanisms include increased rates of enzyme synthesis due to elevated 2E1 mRNA levels, enhanced translation of pre-existing mRNA, or stabilization of ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90049-3
更新日期：1993-04-06 00:00:00
abstract：:Opiates act through a specific receptor to inhibit the striatal adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4,6.1.1] and stimulate a high-affinity GTPase (EC 3.6.1). The present study analyzes the functions of the striatal adenylate cyclase complex following chronic morphine treatment in the rat. The in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90507-2
更新日期：1988-03-15 00:00:00
abstract：:Nucleoside analogs conjugated with galactosyl-terminating peptides selectively enter liver cells and after intracellular release from the carrier partly exit into bloodstream, resulting in higher concentrations in liver blood than in systemic circulation. The aim of the present experiments was to ascertain whether, in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00561-x
更新日期：2001-02-15 00:00:00
abstract：:A compound, YM-53792, was identified as an inhibitor of interleukin-2 (IL-2) gene promoter activity, using a Jurkat cell-based reporter system in which the luciferase gene is regulated by the IL-2 gene promoter. Production of IL-2, interleukin-4 (IL-4) and interleukin-5 (IL-5) from human peripheral blood mononuclear c...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00289-x
更新日期：1997-11-01 00:00:00
abstract：:The deamination of 5-hydroxytryptamine, tryptamine and benzylamine by porcine dental pulp membrane preparations is brought about not only by monoamine oxidase, but also by a clorgyline (and deprenyl) resistant), semicarbazide sensitive enzyme. The semicarbazide sensitive enzyme was also inhibited by aminoguanidine, hy...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90127-7
更新日期：1982-09-01 00:00:00
abstract：:The uptake of iron by the liver and cerebellum was measured in rats using [59Fe]transferrin. An acute ethanol load (50 mmol/kg body wt., i.p.) elicited a significant increase in the hepatic and cerebellar non-heme iron concentration. The uptake of 59Fe by the liver and the cerebellum was significantly greater in the e...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90313-1
更新日期：1994-05-18 00:00:00
abstract：:Rat aortic smooth muscle cells in culture (A-10; ATCC CRL 1476) exhibited low levels of beta-adrenergic receptors as determined by specific binding of [125I]cyanopindolol ([125I]CYP) and marginal stimulation of adenylate cyclase in plasma membranes by (-)isoproterenol. When these cells were exposed to 5 mM sodium buty...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90669-6
更新日期：1986-11-01 00:00:00
abstract：:The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors involved in lipid metabolism and glucose utilization, in cell growth, differentiation and apoptosis, and in the regulation of pro-inflammatory genes expression such as cyclooxygenase-2 (COX-2). PPARγ is the main isoform ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.06.002
更新日期：2014-08-15 00:00:00
abstract：:Naturally occurring amino acid substitutions conferring resistance to methotrexate (MTX) have been reported previously at codon positions 22 (leu-->arg, phe) and 31 (phe-->ser, trp) of mammalian dihydrofolate reductases (DHFR). To explore the character of other substitutions, a polymerase chain reaction (PCR)-assisted...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90393-x
更新日期：1994-03-29 00:00:00
abstract：:Inflammation-induced microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme that synthesizes prostaglandin E(2) (PGE(2)) downstream of cyclooxygenase-2 (COX-2). The efficacy of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors in the treatment of the signs and symptoms of osteoarthritis, rheuma...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.01.003
更新日期：2010-05-15 00:00:00
abstract：:The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90557-1
更新日期：1989-08-15 00:00:00
abstract：:Lipids play a complex role in prostate cancer (PCa). Increased de novo synthesis of fatty acids and/or cholesterol is associated with the development of prostate tumors. Liver X Receptors (LXRs) are members of the nuclear receptor family that regulates intracellular lipid homeostasis. Targeting the transcriptional act...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2013.04.005
更新日期：2013-07-01 00:00:00
