Search results for "dipeptide"

showing 10 items of 99 documents

Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation.

2015

Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation were developed; some of them possess K(i) values in the micromolar range. We studied the structure-activity relationship of these derivatives and we performed docking studies, which allowed us to find out the key interactions established by the inhibitors with the target enzyme. Biological results indicate that the nature of the P2 and P3 substituents and their binding to the S2/S3 pockets is strictly interdependent.

InhibitorMolecular modelCell SurvivalClinical BiochemistryTrypanosoma brucei bruceiAntiprotozoal AgentsPharmaceutical ScienceMolecular modelingCysteine Proteinase InhibitorsBiochemistryCell Linechemistry.chemical_compoundMiceStructure-Activity RelationshipCysteine ProteasesDrug DiscoveryAnimalsMolecular Biology3-Bromo isoxazolinechemistry.chemical_classificationDipeptide-likeDipeptideBinding SitesOrganic ChemistryDipeptidesIsoxazolesCombinatorial chemistryProtein Structure TertiaryMolecular Docking SimulationCysteine EndopeptidasesEnzymeRhodesainchemistryWarheadDocking (molecular)Drug DesignMolecular MedicineRhodesain Dipeptide-like 3-Bromo isoxazoline Inhibitor Molecular modelingBioorganicmedicinal chemistry
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Synthesis and spectroscopic characterization of dicyclohexyltin derivatives of dipeptides, andin vitro effects against MDA-MB 231 breast cancer cells…

1992

Dicyclohexyltin derivatives Cy2SnL (Cy = cyclohexyl) of the dipeptides H2L, glycylglycine, glycylalanine, alanylglycine, glycylvaline, glycylmethionine, glycylphenylalanine and glycyltyrosine, have been obtained by neutralization of Cy2SnO and H2L. The crystal structures of Cy2SnL (L = glycylglycinate, glycylalaninate) have been determined by single X-ray diffraction. Tin in each case has a distorted trigonal bipyramidal environment with the dipeptide acting as a tridentate NNO-ligand. From IR-data, and in some cases from 119Sn Mossbauer and 119Sn NMR data, analogous molecular structures are inferred for the other compounds Cy2SnL. Spectroscopic data indicate that the solid-state structures…

Inorganic ChemistryGlycylglycineTrigonal bipyramidal molecular geometrychemistry.chemical_compoundDipeptidechemistryStereochemistryMössbauer spectroscopyBiological activityGeneral ChemistryCarboxylateNuclear magnetic resonance spectroscopyCrystal structureApplied Organometallic Chemistry
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Semi-empirical MNDO study of the structure of some diorganotin (IV) glycylglycinates

1993

The geometrical structures of some diorganotin glycylglycinates have been obtained using the MNDO semi-empirical method. A good agreement with the experimental diffractometric data was found.

Inorganic Chemistrychemistry.chemical_compoundDipeptideChemistryComputational chemistryStereochemistryMNDOGeneral ChemistryCarboxylateApplied Organometallic Chemistry
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Conformational Analysis of beta-Lactam-Containing Ferrocene Peptides

2009

The homochiral 3-amino-1-(4-methoxyphenyl)-4-phenyl-beta-lactam (≡ Alm) was conjugated with Boc-Ala giving Ala-Alm (9) after Boc-deprotection (Boc = tert-butoxycarbonyl, Ala = alanine). Coupling of FcCOOH (1) and Boc-Fca (10) with “ dipeptide” 9 resulted in the formation of FcCO-Ala-Alm (12) and the trisamide Boc-Fca-Ala-Alm (13), respectively (Fc = ferrocenyl, Fca = 1’ -aminoferrocene-1-carboxylic acid). The reactions were accomplished by the HOBt/EDC procedure and the products were obtained in good yields (HOBt = 1-hydroxybenzotriazole, EDC = N-(3-dimethylaminopropyl)-N’ -ethylcarbodiimide hydrochloride). Symmetrically 1, 1’ -disubstituted “ tetrapeptide” Fn(CO-Ala-Alm)2 (14) was prepared…

Inorganic Chemistryconformation analysis ; density functional calculations ; hydrogen bonds ; metallocenes ; molecular modelingchemistry.chemical_compoundDipeptidechemistryMolecular modelTetrapeptideFerroceneHydrogen bondStereochemistryIntramolecular forceLactamConjugated system
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Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat

2018

Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters,…

Male0301 basic medicinePhenylalaninePotassiumchemistry.chemical_elementPharmacologyHippocampal formationCalciumInhibitory postsynaptic potentialHippocampusSettore BIO/09 - Fisiologia03 medical and health sciencesantiepileptic drug0302 clinical medicineDrug DiscoveryN-valproyl-L-tryptophanvalproic acid.medicineAnimalshippocampal epilepsyRats WistarPharmacologyValproic AcidEpilepsyValproyl-L-Phenylalanine (VPA-Phen)Dipeptidesinterictal burstRat brainAmino-acidic derivativeRats030104 developmental biologychemistryAnticonvulsantslipids (amino acids peptides and proteins)030217 neurology & neurosurgerymedicine.drugN-valproyl-L-phenylalanineCurrent Pharmaceutical Design
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Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors

2011

The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled recep…

MaleReceptors Vasopressinendocrine system diseasesReceptor for Advanced Glycation End Productslcsh:MedicineHydroxamic Acids570 Life sciencesRAGE (receptor)Adenylyl cyclaseADAM10 ProteinMicePhosphatidylinositol 3-Kinaseschemistry.chemical_compoundMolecular Cell BiologyNeurobiology of Disease and RegenerationSignaling in Cellular ProcessesMembrane Receptor SignalingReceptors Immunologiclcsh:ScienceReceptorLungCellular Stress ResponsesCalcium signalingMultidisciplinaryKinaseDipeptidesHormone Receptor SignalingCell biologyMatrix Metalloproteinase 9NeurologyReceptors OxytocinGene Knockdown Techniquescardiovascular systemMatrix Metalloproteinase 2Pituitary Adenylate Cyclase-Activating PolypeptideMedicineRNA InterferenceAdenylyl CyclasesResearch ArticleSignal Transduction570 Biowissenschaftenmedicine.medical_specialtyMAP Kinase Signaling SystemADAM17 ProteinBiologyAlzheimer DiseaseCa2+/calmodulin-dependent protein kinaseInternal medicinemedicineAnimalsHumansProtease InhibitorsCalcium Signalingcardiovascular diseasesBiologyG protein-coupled receptorlcsh:RHEK 293 cellsMembrane Proteinsnutritional and metabolic diseasesCyclic AMP-Dependent Protein KinasesADAM ProteinsG-Protein SignalingHEK293 CellsEndocrinologychemistryProteolysisDementialcsh:QAmyloid Precursor Protein SecretasesMolecular Neurosciencehuman activitiesReceptors Pituitary Adenylate Cyclase-Activating Polypeptide Type INeurosciencePLoS ONE
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Inhibitory effects of N-valproyl-L-tryptophan on high potassium, low calcium and low magnesium-induced CA1 hippocampal epileptiform bursting activity…

2012

N-valproyl-l-tryptophan (VPA-Tryp), new antiepileptic drug, was tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 or 2 mM) of Valproate (VPA) or VPA-Tryp. Both burst duration and interburst frequency during and after treatment were off-line compared with baseline values. For both parameters, the latency and the length of statistically significant response periods as well as the magnitude of drug-induced responses were calculated. VPA-Tryp evoked fewer and weaker early excitatory effects than VPA on …

Maleantiepileptic drug valproic acidPotassiumchemistry.chemical_elementAction PotentialsCalciumHippocampal formationPharmacologyIn Vitro TechniquesInhibitory postsynaptic potentialSettore BIO/09 - Fisiologiaamino-acidic derivativeBurstingmedicineReaction Timehippocampal epilepsyAnimalsDrug InteractionsMagnesiumRats WistarCA1 Region HippocampalBiological PsychiatryValproic AcidAnalysis of VarianceDose-Response Relationship DrugMagnesiumDipeptidesElectric StimulationRatsPsychiatry and Mental healthNeurologychemistrySettore CHIM/09 - Farmaceutico Tecnologico ApplicativoExcitatory postsynaptic potentialPotassiuminterictal burstslipids (amino acids peptides and proteins)AnticonvulsantsNeurology (clinical)medicine.drugJournal of neural transmission (Vienna, Austria : 1996)
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Kidney donors and kidney transplants have abnormal aminothiol redox status, and are at increased risk of oxidative stress and reduced redox buffer ca…

2013

Abstract Objective Living kidney donors have been part of a successful kidney transplant programme in Norway for almost 50 years. Glomerular filtration rates (GFRs) have tended to remain stable at about 70% of pre-donation levels. Plasma total homocysteine (Hcy) has an inverse relationship to kidney function, and previous reports indicate elevated levels of Hcy in kidney donors. We wanted to examine the most important plasma aminothiols in kidney donors, i.e. Hcy, cysteine (Cys) and cysteinylglycine (CG) with their redox species. The aminothiol redox-system appears to be an integral part of the extracellular antioxidant defence system in the body. Design and methods Plasma concentrations of…

Malemedicine.medical_specialtyAntioxidantHomocysteinemedicine.medical_treatmentClinical BiochemistryRenal functionBuffersmedicine.disease_causeRedoxPreeclampsiachemistry.chemical_compoundRisk FactorsInternal medicineLiving DonorsmedicineExtracellularHumansCysteineSulfhydryl CompoundsHomocysteineDemographyKidneyurogenital systemDipeptidesGeneral MedicineMiddle Agedmedicine.diseaseKidney TransplantationOxidative StressEndocrinologymedicine.anatomical_structurechemistryCase-Control StudiesFemaleOxidation-ReductionOxidative stressClinical Biochemistry
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Decreased level of cardiac antioxidants in endurance-trained rats.

1989

Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and i…

Malemedicine.medical_specialtyAntioxidantPhysiologymedicine.medical_treatmentGlutathione reductasePhysical ExertionAntioxidantsEndurance trainingInternal medicinemedicineAnimalsSwimmingchemistry.chemical_classificationbiologyGlutathione peroxidaseVitamin EMyocardiumRats Inbred StrainsDipeptidesRatsmedicine.anatomical_structureEndocrinologychemistryPeroxidasesVentricleCatalaseCirculatory systembiology.proteinPhysical EnduranceOxidoreductasesActa physiologica Scandinavica
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Sequential Treatment Escalation with Dapagliflozin and Saxagliptin Improves Beta Cell Function in Type 2 Diabetic Patients on Previous Metformin Trea…

2018

AbstractWe investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.0 years; duration of diabetes 8.8±4.7 years; HbA1c 63.9±15.8 mmol/mol; mean±SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2). At baseline and at the end of each treatment period, fasting glucose and insulin levels were analysed, and a hyperglycaemic clam…

Malemedicine.medical_specialtyEndocrinology Diabetes and Metabolismmedicine.medical_treatmentClinical BiochemistryAdamantane030209 endocrinology & metabolism030204 cardiovascular system & hematologySaxagliptinBiochemistryGlucagon03 medical and health scienceschemistry.chemical_compound0302 clinical medicineEndocrinologyInsulin resistanceDouble-Blind MethodGlucosidesInsulin-Secreting CellsInternal medicineDiabetes mellitusmedicineHumansBenzhydryl CompoundsDapagliflozinAgedProinsulinbusiness.industryInsulinBiochemistry (medical)DipeptidesGeneral MedicineMiddle Agedmedicine.diseaseMetforminEndocrinologyDiabetes Mellitus Type 2chemistryFemalebusinessmedicine.drugHormone and Metabolic Research
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