Abstract:
:In an effort to obtain highly potent glucagon antagonists, we have investigated glucagon (1) structure-function relationships utilizing the following design principles: (1) structural changes known to lead to partial agonist activities; (2) conformational restrictions; (3) changes in the conformational probabilities of the primary sequence; and (4) increased amphiphilicity. In this report we present the total synthesis, purification, receptor binding, adenylate cyclase activity, in vivo glycogenolytic activity and CD spectrum of the following four glucagon analogues: [Ahx17,18]glucagon (2), [D-Phe4,Tyr5, 3,5-diiodo-Tyr10,Arg12,Lys17,18,Glu21]glucagon (3), [Asp9,Lys12,Lys17,18,Glu21]glucagon 4, and [Glu15,Lys17,18]glucagon 5. Compound 2 binds exclusively to the high affinity receptor and compound 3 was a highly potent antagonist with respect to adenylate cyclase activity. Analog 4 showed distinct biphasic binding (IC50 5.6 nM and 630 nM), with only the low affinity binding leading to adenylate cyclase activity. Furthermore in analogue 5 receptor binding and adenylate cyclase activity were dissociated by a factor of 5. The results are consistent with a multistep binding mechanism in which glucagon interacts first nonspecifically with the anisotropic interphase of the cell membrane, followed by a conformational transition which occurs in the sequences 10-14 and 15-18 when the membrane bound peptide binds to its receptor.
journal_name
Life Scijournal_title
Life sciencesauthors
Hruby VJ,Gysin B,Trivedi D,Johnson DGdoi
10.1016/0024-3205(93)90513-3subject
Has Abstractpub_date
1993-01-01 00:00:00pages
845-55issue
10eissn
0024-3205issn
1879-0631pii
0024-3205(93)90513-3journal_volume
52pub_type
杂志文章相关文献
LIFE SCIENCES文献大全abstract::NSAIDs can elevate blood pressure through mechanisms such as renal vasoconstriction and sodium retention. These effects are particularly evident in hypertensive individuals. Nitric oxide-releasing NSAID derivatives have been shown to have greatly reduced toxicity in the gastrointestinal tract and kidney. We therefore ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(98)00072-1
更新日期:1998-01-01 00:00:00
abstract::We contrast the effects of three intermediate electron acceptors (IEAs) on the highly quantitative ESTA bioassay for human growth hormone. This is a microculture tetrazolium assay based upon the in vitro reduction of the tetrazolium salt MTT, by Nb2 cells which have been activated with hGH. Each of the IEAs influenced...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(96)00512-7
更新日期:1996-01-01 00:00:00
abstract::The effects of erythropoietin (EPO) on cytosolic free calcium concentration ([Ca2+]i) in platelets of 20 essential hypertensive patients (HT) and of 25 normotensive subjects (NT) were investigated using the fura2 technique. In resting platelets [Ca2+]i were not significantly higher in HT compared to NT (74.3 +/- 7.8 n...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(92)90010-m
更新日期:1992-01-01 00:00:00
abstract:AIMS:This study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties. MAIN METHODS:APOE null mice at 6 and 15weeks of age were treated with melatonin at a dose of 0.1mg/kg/day or 10mg/kg/day. We evalua...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2012.11.011
更新日期:2013-05-20 00:00:00
abstract::In the present study the effects of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) on fibroblast growth and activity have been studied. In this regard the AA have evaluated in primary cultures of human gengival normal fibroblasts (PG1 cells): a)-the expression of GM-CSF receptor (GM-CSFR) (alfa unit) on the...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(98)00281-1
更新日期:1998-01-01 00:00:00
abstract::Respiring mitochondria represent the major source of superoxide production in most cells, and superoxide anions function as direct precursors of hydrogen peroxide formation within mitochondria. We use a lucigenen-derived chemiluminescence (LDCL) assay to test the hypothesis that intramitochondrial superoxide productio...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(02)01538-2
更新日期:2002-05-03 00:00:00
abstract:AIMS:As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS:A systematic review of the lit...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2020.117788
更新日期:2020-08-01 00:00:00
abstract::Unfertilized ova from Shad, a North Atlantic herring, contains a cytostatic inhibitor of T lymphocyte blastogenesis. The inhibitor has an estimated molecular weight of 10,000-30,000 Da, is heat stable, non dialyzable, and resistant to protease digestion and periodate oxidation. Although the inhibitor functions at an e...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(90)90336-p
更新日期:1990-01-01 00:00:00
abstract::Gloriosaols A-C, isolated from Yucca gloriosa (Agavaceae), are novel phenolic compounds structurally related to resveratrol. In the present study, we show that gloriosaols possess antiproliferative and pro-apoptotic activity on tumor cells of different histogenetic origin and that their cell growth inhibition potentia...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2007.07.010
更新日期:2007-08-23 00:00:00
abstract::The present study was designed to investigate the effect of partial (two-thirds) hepatectomy (PH) on hepatic and intestinal glutathione S-transferases (GSTs) activities. A significant decrease of cytosolic hepatic GSTs activity was observed after the PH. The lowest value of hepatic GSTs was obtained 48 h after the sur...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(95)02024-d
更新日期:1995-01-01 00:00:00
abstract::Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested fro...
journal_title:Life sciences
pub_type: 杂志文章,评审
doi:10.1016/j.lfs.2005.09.005
更新日期:2005-12-22 00:00:00
abstract::Phospholipase C (PLC), an enzyme involved in the hydrolysis of membrane phospholipid- phosphatidylinositol-bisphosphate to inositol triphosphate and diacylglycerol, and Phorbol 12, myristate 13, acetate (PMA), a tumor promoting agent, could significantly stimulate testosterone (T) secretion from Leydig cells. Arachido...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(87)90223-2
更新日期:1987-07-27 00:00:00
abstract::C57BL6/J (B6) mice lacking Se-dependent GSH peroxidase 1 and 2 (GPx1/2-DKO) develop mild to moderate ileocolitis around weaning. These DKO mice have a disease resembling human very-early-onset inflammatory bowel disease (VEOIBD), which is associated with mutations in NADPH oxidase genes. Drugs including dexamethasone ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2019.116884
更新日期:2019-12-15 00:00:00
abstract::The purpose of this study was to investigate the involvement of calcium in K+ currents and its effects on amino acid accumulation and on the membrane potential regulated by tri-iodo-L-thyronine (T3) in Sertoli cells. Immature rat testes were pre-incubated for 30 min in Krebs-Ringer bicarbonate buffer and incubated for...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2003.08.005
更新日期:2004-01-23 00:00:00
abstract::Incubation of unfixed, frozen sections of rat pancreas with tritiated guanidinoethylmercaptosuccinic acid (GEMSA) resulted in a localization of [3H]-GEMSA autoradiographic grains over the islets of Langerhans, suggesting that a carboxypeptidase H-like enzyme occurs in the islet. ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(87)90072-5
更新日期:1987-06-29 00:00:00
abstract::P120-catenin (P120) was known to function in adhesion between cells and signal transduction in many types of cells. In this study, we investigated the expression and role of P120 in pulmonary fibrosis and transforming growth factor beta (TGF-β) mediated lung fibroblast-to-myofibroblast differentiation (fibroblast diff...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2019.05.052
更新日期:2019-08-01 00:00:00
abstract::In an attempt to investigate the role of nucleoside transporter function in the hypertensive state, we have compared the binding of [3H]nitrobenzylthioinosine ([3H]NBMPR), a nucleoside transporter probe, in membranes prepared from platelet, renal, pulmonary, cardiac and brain tissues of spontaneously hypertensive rats...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(90)90024-l
更新日期:1990-01-01 00:00:00
abstract::As a decrease in cholinergic neurons has been observed in Alzheimer's Disease (AD), therapeutic approaches to AD include inhibition of acetylcholinesterase to increase acetylcholine levels. Evidence suggests that acetylcholine release in the CNS is modulated by negative feedback via presynaptic M2 receptors, blockade ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(98)00598-0
更新日期:1999-01-01 00:00:00
abstract::In order to estimate the intestinal stability of ebiratide [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], a novel adrenocorticotropic hormone (ACTH) analogue, after oral administration, the hydrolytic properties of ebiratide were determined in the rat small intestinal fluid and mucosal homogenates. Ebiratide was extr...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(94)00674-1
更新日期:1994-01-01 00:00:00
abstract::The effects of pyrroloquinoline quinone (PQQ) and PQQ-oxazole (PQQ-glycine adduct) on DNA synthesis were examined using cultured human fibroblasts. Confluent fibroblasts were cultured in serum-free Dulbecco's modified Eagle's media, and various concentrations of PQQ and PQQ-oxazole were added to the media. After incub...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(93)90631-c
更新日期:1993-01-01 00:00:00
abstract::The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the f...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2004.03.030
更新日期:2004-09-10 00:00:00
abstract::Physalis angulata and P. peruviana are herbs widely used in folk medicine. In this study, the aqueous and ethanol extracts prepared from the whole plant of these species were evaluated for their antihepatoma activity. Using XTT assay, three human hepatoma cells, namely Hep G2, Hep 3B and PLC/PRF/5 were tested. The res...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2003.09.058
更新日期:2004-03-05 00:00:00
abstract::An animal model of haloperidol-induced tardive dyskinesia was studied in relation to the dietary manipulation of tryptophan and its effect on the movement disorder. This study showed a significant negative behavioral response to the neuroleptic drug, haloperidol. Increased dietary tryptophan (1.0 vs. 0.3%) significant...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(87)90602-3
更新日期:1987-10-05 00:00:00
abstract:AIMS:Changes in cardiac autonomic nervous function have been evaluated by studying the related indexes of heart rate variability (HRV) in patients with focal epilepsy (FE) in the interictal period. MAIN METHODS:A total of 30 FE patients who were treated in our department from July 2015 to May 2017, were included into ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2018.08.033
更新日期:2018-09-15 00:00:00
abstract:AIMS:The aim of the present study was to investigate the protective effects of AGK2 as a selective SIRT2 inhibitor on thioacetamide (TAA)-induced acute liver failure (ALF) in mice and its potential mechanism. MAIN METHODS:All male C57BL/6 mice were separated into control, TAA, AGK2 + TAA, and AGK2 groups. The histolog...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2019.05.061
更新日期:2019-08-01 00:00:00
abstract:INTRODUCTION AND AIM:Wound healing is an orderly complex process involving inflammation, clotting, re-epithelialization, neovascularization and wound closure. In diabetic patients, such process is impaired and delayed, posing negative economic as well as social consequences. Diabetex, (patency# EP 0877617 A1) composed ...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/j.lfs.2018.06.020
更新日期:2018-08-15 00:00:00
abstract::The influence of different, nitric oxide-containing ruthenium complexes on the evoked potentials recorded from the CA1 region of the mouse hippocampus in vitro has been investigated. Of the compounds tested, only trans-[(NO)(P(OEt)3)(NH3)4Ru](PF6)3 (1-2.5 mM) exerted a strong facilitatory action on the population spik...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/s0024-3205(01)00951-1
更新日期:2001-02-16 00:00:00
abstract::We used in vitro quantitative autoradiography to investigate changes in neurotransmitter receptor binding, including muscarinic cholinergic, PCP, GABAA, benzodiazepine, D1 and 5-HT2A receptor, in the brains of aged rats, compared with such binding in young rats. Scatchard analysis revealed that the maximal number of b...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(94)00320-3
更新日期:1994-01-01 00:00:00
abstract::The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) th...
journal_title:Life sciences
pub_type: 杂志文章
doi:10.1016/0024-3205(90)90157-m
更新日期:1990-01-01 00:00:00
abstract:AIM:This study investigated the effect of voluntary motor effort during a low-intensity (30% maximal voluntary contraction [MVC]) muscle exercise training program on increasing muscle strength. MATERIALS AND METHODS:Eighteen young and healthy individuals were randomly assigned to one of three groups: high mental effor...
journal_title:Life sciences
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.lfs.2017.04.003
更新日期:2017-06-01 00:00:00