Academic literature on the topic 'Antagonists'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Antagonists.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Antagonists"
1
Otto-Hanson, L. K., Z. Grabau, C. Rosen, C. E. Salomon, and L. L. Kinkel. "Pathogen Variation and Urea Influence Selection and Success of Streptomyces Mixtures in Biological Control." Phytopathology® 103, no. 1 (January 2013): 34–42. http://dx.doi.org/10.1094/phyto-06-12-0129-r.
Full textAbstract:
Success in biological control of plant diseases remains inconsistent in the field. A collection of well-characterized Streptomyces antagonists (n = 19 isolates) was tested for their capacities to inhibit pathogenic Streptomyces scabies (n = 15 isolates). There was significant variation among antagonists in ability to inhibit pathogen isolates and among pathogens in their susceptibility to inhibition. Only one antagonist could inhibit all pathogens, and antagonist–pathogen interactions were highly specific, highlighting the limitations of single-strain inoculum in biological control. However, the collection of pathogens could be inhibited by several combinations of antagonists, suggesting the potential for successful antagonist mixtures. Urea generally increased effectiveness of antagonists at inhibiting pathogens in vitro (increased mean inhibition zones) but its specific effects varied among antagonist–pathogen combinations. In greenhouse trials, urea enhanced the effectiveness of antagonist mixtures relative to individual antagonists in controlling potato scab. Although antagonist mixtures were frequently antagonistic in the absence of urea, all n= 2 and n = 3 antagonist–isolate combinations were synergistic in the presence of urea. This work provides insights into the efficacy of single- versus multiple-strain inocula in biological control and on the potential for nutrients to influence mixture success.
2
Dilger, James P., Ana Maria Vidal, Man Liu, Claire Mettewie, Takahiro Suzuki, Anh Pham, and Deeptankar Demazumder. "Roles of Amino Acids and Subunits in Determining the Inhibition of Nicotinic Acetylcholine Receptors by Competitive Antagonists." Anesthesiology 106, no. 6 (June 1, 2007): 1186–95. http://dx.doi.org/10.1097/01.anes.0000267602.94516.7f.
Full textAbstract:
Background Binding sites for agonists and competitive antagonists (nondepolarizing neuromuscular blocking agents) are located at the alpha-delta and alpha-epsilon subunit interfaces of adult nicotinic acetylcholine receptors. Most information about the amino acids that participate in antagonist binding comes from binding studies with (+)-tubocurarine and metocurine. These bind selectively to the alpha-epsilon interface but are differentially sensitive to mutations. To test the generality of this observation, the authors measured current inhibition by five competitive antagonists on wild-type and mutant acetylcholine receptors. Methods HEK293 cells were transfected with wild-type or mutant (alphaY198F, epsilonD59A, epsilonD59N, epsilonD173A, epsilonD173N, deltaD180K) mouse muscle acetylcholine receptor complementary DNA. Outside-out patches were excised and perfused with acetylcholine in the absence and presence of antagonist. Concentration-response curves were constructed to determine antagonist IC50. An antagonist-removal protocol was used to determine dissociation and association rates. Results Effects of mutations were antagonist specific. alphaY198F decreased the IC50 of (+)-tubocurarine 10-fold, increased the IC50 of vecuronium 5-fold, and had smaller effects on other antagonists. (+)-Tubocurarine was the most sensitive antagonist to epsilonD173 mutations. epsilonD59 mutations had large effects on metocurine and cisatracurium. deltaD180K decreased inhibition by pancuronium, vecuronium, and cisatracurium. Inhibition by these antagonists was increased for receptors containing two delta subunits but no epsilon subunit. Differences in IC50 arose from differences in both dissociation and association rates. Conclusion Competitive antagonists exhibited different patterns of sensitivity to mutations. Except for pancuronium, the antagonists were sensitive to mutations at the alpha-epsilon interface. Pancuronium, vecuronium, and cisatracurium were selective for the alpha-delta interface. This suggests the possibility of synergistic inhibition by pairs of antagonists.
3
Presti, M. E., and J. D. Gardner. "Receptor antagonists for gastrointestinal peptides." American Journal of Physiology-Gastrointestinal and Liver Physiology 264, no. 3 (March 1, 1993): G399—G406. http://dx.doi.org/10.1152/ajpgi.1993.264.3.g399.
Full textAbstract:
Receptors for gastrointestinal peptides are all G protein-coupled receptors. Since the discovery that dibutyryl guanosine 3',5'-cyclic monophosphate was a cholecystokinin-receptor antagonist, a variety of receptor antagonists have been developed for a number of different gastrointestinal peptides. These antagonists have been useful in classifying receptors for gastrointestinal peptides and in elucidating complex regulation of gastrointestinal function. Some antagonists also have therapeutic potential. Based on the receptors with which they interact, gastrointestinal peptides can be grouped into families, and, in general, a given receptor antagonist is specific for a given family. This review covers the different families of gastrointestinal peptides and the major antagonists that exist for each family.
4
Robben, J. H., M. Sze, N. V. A. M. Knoers, and P. M. T. Deen. "Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus." American Journal of Physiology-Renal Physiology 292, no. 1 (January 2007): F253—F260. http://dx.doi.org/10.1152/ajprenal.00247.2006.
Full textAbstract:
Intracellular retention of a functional vasopressin V2 receptor (V2R) is a major cause of congenital nephrogenic diabetes insipidus (NDI) and rescue of V2R mutants by nonpeptide antagonists may restore their basolateral membrane (BM) localization and function. However, the criteria for efficient functional rescue of G protein-coupled receptor (GPCR) mutants at clinically feasible antagonist concentrations are unknown. We found that the four nonpeptide antagonists SR49059, OPC31260 , OPC41061 , and SR121463B induced maturation and rescued the BM expression of eight of nine different V2R mutants, stably expressed in physiologically relevant polarized cells. The extent of maturation and rescued BM expression correlated with the antagonists' concentration and affinity for the V2R. Displacement of the antagonists by AVP and subsequent cAMP generation inversely correlated with the antagonists' affinities for the V2R but is partially influenced by antagonist-specific aspects. Despite limited increases in maturation and cell-surface expression of V2R mutants, the low-affinity SR49059 optimally induced functional rescue at high concentrations, due to its easy displacement by vasopressin. At clinically feasible antagonist concentrations, however, only the high-affinity antagonists OPC31260 and OPC41061 induced functional rescue, as at these concentrations the extent of BM expression became limited. In conclusion, functional rescue of mutant V2Rs at clinically feasible concentrations is most effective with high-affinity antagonists. As OPC31260 and OPC41061 are clinically safe, they are promising candidates to relieve NDI. Moreover, as numerous other diseases are caused by endoplasmic reticulum-retained GPCRs for which cell-permeable antagonists become available, our finding that high-affinity antagonists are superior is anticipated to be important for pharmacotherapy development of these diseases.
5
Okada, H., H. Suzuki, Y. Kanno, Y. Yamamura, and T. Saruta. "Chronic and selective vasopressin blockade in spontaneously hypertensive rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 6 (December 1, 1994): R1467—R1471. http://dx.doi.org/10.1152/ajpregu.1994.267.6.r1467.
Full textAbstract:
Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.
6
Barth, Francis, and Murielle Rinaldi-Carmona. "The Development of Cannabinoid Antagonists." Current Medicinal Chemistry 6, no. 8 (August 1999): 745–55. http://dx.doi.org/10.2174/0929867306666220401143808.
Full textAbstract:
The discovery of two distinct cannabinoid receptors (CB1 and C B 2 ) in the early 1990's has revived the research on cannabinoid antagonists. While the search for antagonists based on the structure of agonists (classical cannabinoids or aminoalkylindoles) appeared rather disappointing, the first potent cannabinoid antagonists were developed in a new chemical series: the diarylpyrazoles. Since its discovery in 1994, the selective CB1 antagonist SR 141716 has become a major pharmacological tool to elucidate the physiological role of the CB 1 cannabinoid receptor and its endogenous ligand. The selective CB2 antagonist SR 144528 is expected to play the same role for the CB2 receptors, while the recent development of cannabinoid antagonists belonging to other chemical series illustrates the interest of these compounds which are now considered as interesting therapeutic targets by many pharmaceutical companies.
7
Schulz, Ashley N., Rima D. Lucardi, and Travis D. Marsico. "Successful Invasions and Failed Biocontrol: The Role of Antagonistic Species Interactions." BioScience 69, no. 9 (August 7, 2019): 711–24. http://dx.doi.org/10.1093/biosci/biz075.
Full textAbstract:
Abstract Understanding the successes and failures of nonnative species remains challenging. In recent decades, researchers have developed the enemy release hypothesis and other antagonist hypotheses, which posit that nonnative species either fail or succeed in a novel range because of the presence or absence of antagonists. The premise of classical biological control of invasive species is that top-down control works. We identify twelve existing hypotheses that address the roles that antagonists from many trophic levels play during plant and insect invasions in natural environments. We outline a unifying framework of antagonist hypotheses to simplify the relatedness among the hypotheses, incorporate the role of top-down and bottom-up influences on nonnative species, and encourage expansion of experimental assessments of antagonist hypotheses to include belowground and fourth trophic level antagonists. A mechanistic understanding of antagonists and their impacts on nonnative species is critical in a changing world.
8
Bödder, Johanna, Leanne M. Kok, Jonathan A. Fauerbach, Georgina Flórez-Grau, and I. Jolanda M. de Vries. "Tailored PGE2 Immunomodulation of moDCs by Nano-Encapsulated EP2/EP4 Antagonists." International Journal of Molecular Sciences 24, no. 2 (January 11, 2023): 1392. http://dx.doi.org/10.3390/ijms24021392.
Full textAbstract:
Prostaglandin E2 (PGE2) is an important maturation mediator for dendritic cells (DCs). However, increased PGE2 levels in the tumor exert immunosuppressive effects on DCs by signaling through two E-Prostanoid (EP) receptors: EP2 and EP4. Blocking EP-receptor signaling of PGE2 with antagonists is currently being investigated for clinical applications to enhance anti-tumor immunity. In this study, we investigated a new delivery approach by encapsulating EP2/EP4 antagonists in polymeric nanoparticles. The nanoparticles were characterized for size, antagonist loading, and release. The efficacy of the encapsulated antagonists to block PGE2 signaling was analyzed using monocyte-derived DCs (moDCs). The obtained nanoparticles were sized between 210 and 260 nm. The encapsulation efficacy of the EP2/EP4 antagonists was 20% and 17%, respectively, and was further increased with the co-encapsulation of both antagonists. The treatment of moDCs with co-encapsulation EP2/EP4 antagonists prevented PGE2-induced co-stimulatory marker expression. Even though both antagonists showed a burst release within 15 min at 37 °C, the nanoparticles executed the immunomodulatory effects on moDCs. In summary, we demonstrate the functionality of EP2/EP4 antagonist-loaded nanoparticles to overcome PGE2 modulation of moDCs.
9
Geling, Olga, and Hans-Georg Eichler. "Should 5-Hydroxytryptamine-3 Receptor Antagonists Be Administered Beyond 24 Hours After Chemotherapy to Prevent Delayed Emesis? Systematic Re-Evaluation of Clinical Evidence and Drug Cost Implications." Journal of Clinical Oncology 23, no. 6 (February 20, 2005): 1289–94. http://dx.doi.org/10.1200/jco.2005.04.022.
Full textAbstract:
Purpose 5-Hydroxytryptamine-3 receptor antagonists (5-HT3 antagonists) are effective for preventing acute chemotherapy-induced emesis but the benefits of continuing administration of these agents beyond 24 hours after chemotherapy (delayed emesis) remain unclear. The purpose of this study was to provide estimates of clinical efficacy and drug acquisition cost associated with administering 5-HT3 antagonists beyond 24 hours, as monotherapy or as added to dexamethasone. Methods This analysis is based on the Cancer Care Ontario Practice Guidelines Initiative meta-analysis of the efficacy of 5-HT3 antagonists. Results from the clinical trials covered in that meta-analysis were reanalyzed to provide estimates of absolute risk reductions (ARR) and numbers needed to treat (NNT) for 5-HT3 antagonists, as monotherapy or as adjunct treatment. Numbers of 5-HT3 antagonist unit doses per successfully treated patient were also calculated. Results Five studies (comprising 1,716 assessable patients) compared a 5-HT3 antagonist with placebo; five studies (2,240 patients) compared a combination of a 5-HT3 antagonist and dexamethasone with dexamethasone monotherapy. ARR for monotherapy was only 8.2% (95% CI, 3.0% to 13.4%). On average, 74 5-HT3 antagonist doses must be administered to 12 patients (NNT, 12.2; 95% CI, 7.5 to 33.4) not receiving dexamethasone to protect one patient from delayed emesis. In those patients receiving dexamethasone as standard antiemetic treatment in the delayed phase, the addition of a 5-HT3 antagonist did not significantly improve control of delayed emesis as compared with dexamethasone monotherapy (ARR, 2.6%; 95% CI, −0.6% to 5.8%). Conclusion Neither clinical evidence nor considerations of cost effectiveness justify using 5-HT3 antagonists beyond 24 hours after chemotherapy for prevention of delayed emesis.
10
Varma, Daya R. "Ligand-independent negative chronotropic responses of rat and mouse right atria to β-adrenoceptor antagonists." Canadian Journal of Physiology and Pharmacology 77, no. 12 (November 15, 1999): 943–49. http://dx.doi.org/10.1139/y99-099.
Full textAbstract:
Negative chronotropic effects of β-adrenoceptor (βAR) antagonists on right atria from reserpine-treated rats and mice were determined as a test of their inverse agonist activities. β2AR antagonist ICI-118,551 and nonselective βAR antagonists alprenolol, propranolol, and timolol produced negative chronotropic effects. In contrast, nonselective βAR antagonists pindolol and nadolol as well as β1AR-selective antagonists atenolol, acebutolol, and metoprolol did not cause a significant decrease in atrial rates. The neutral antagonist pindolol but not the inverse agonist alprenolol inhibited the negative chronotropic activities of ICI-118,551. Isoprenaline, salbutamol, and noradrenaline produced positive chronotropic effects; the chronotropic effects of isoprenaline and salbutamol but not of noradrenaline were antagonized by ICI-118,551. It is concluded that both β1AR and β2AR mediate positive chronotropic effects of catecholamines on rat and mouse atria but only β2AR are constitutively active.Key words: inverse agonism, ICI-118,551, β1 adrenoceptor-selective antagonists, chronotropic responses, catecholamines.
Dissertations / Theses on the topic "Antagonists"
1
Horn, Johanna. "Calcium antagonists in stroke." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2001. http://dare.uva.nl/document/58263.
Full text
2
Paoletta, Silvia. "Designing adenosine receptors antagonists using an in silico approach." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422906.
Full textAbstract:
The neuromodulator adenosine affects a wide variety of physiopathological processes through activation of four receptors, classified as A1, A2A, A2B, and A3 subtypes. Adenosine receptors (ARs) belong to family A of G protein-coupled receptors (GPCRs) and are ubiquitously expressed in the human body. Activation or blockade of ARs is responsible for a wide range of effects in numerous organ systems; and therefore the regulation of ARs can have many potential therapeutic applications.
The main objective of this project has been the investigation of the in silico molecular pharmacology of adenosine receptors and, in particular, of the human A2A and A3 adenosine receptors to guide the discovery and the structural refinement of new potent and selective AR antagonists.
The recently published crystal structures of the human A2A adenosine receptor (hA2AAR) provide detailed three-dimensional information useful to support homology modeling studies and receptor-based drug design approaches. In particular, the 2.6 Å crystallographic structure of the hA2AAR in complex with the potent and selective antagonist ZM241385 was used as template to build a homology model of the hA3AR.
In order to validate the molecular docking protocols for the adenosine receptors family, the hA2AAR crystal structure was used to perform in parallel
molecular docking studies using different docking software. Then RMSD values between predicted and crystallographic poses of ZM241385 were calculated to select the docking protocol able to better reproduce this molecular system and to be used in the following molecular docking studies.
Subsequently, molecular docking studies of different ARs antagonists were performed at the hA3AR model and at the hA2AAR crystal structure, enabling the exploration of the potential effects of chemical modifications of these compounds, and thus facilitating the lead optimization process. Different series of new compounds belonging to known adenosine antagonists classes, including triazolo-triazines and pyrazolo-triazolo-pyrimidines, have been analyzed and modified with the aim to modulate their affinity towards different adenosine receptor subtypes, to increase their solubility, or to overcome their metabolic instability. Moreover, several compounds with simplified scaffolds have been proposed as new adenosine receptor antagonists; such as pyrazolo-pyrimidinones, phthalazinones and triazolo-pyrimidines.
Finally, the knowledge gained through the docking studies led to the identification of structural features of antagonist compounds important for the interaction with the hA3AR and was applied to the design of fluorescent ligands for this subtype, of particular interest as pharmacological probes.
In conclusion, the integration of in silico studies with synthetic work and pharmacological tests resulted to be a good strategy for the development of new compounds as adenosine receptors antagonists and led to a better understanding at the molecular level of this class of GPCRs.L’adenosina è un neuromodulatore che regola molti processi fisiopatologici attraverso l’attivazione di quattro diversi recettori accoppiati a proteine G (GPCRs), classificati come sottotipi A1, A2A, A2B e A3. I recettori adenosinici sono ubiquitari nell’organismo umano e la loro attivazione è responsabile di numerosi effetti in diversi organi. Proprio per questo motivo la regolazione dell’attività di questi recettori può avere interessanti applicazioni terapeutiche. Il principale obiettivo di questo progetto è stato l’analisi in silico a livello molecolare dei recettori adenosinici, ed in particolare dei recettori adenosinici umani A2A e A3, per guidare la scoperta e l’ottimizzazione strutturale di nuovi antagonisti adenosinici potenti e selettivi. Le strutture cristallografiche del recettore adenosinico umano A2A, recentemente pubblicate, forniscono dettagliate informazioni strutturali utili per supportare studi di homology modeling e approcci di drug design di tipo structure-based. In particolare, la struttura cristallografica del recettore adenosinico umano A2A, in complesso con l’antagonista potente e selettivo ZM241385, è stata utilizzata come templato per la costruzione di un modello per omologia del recettore adenosinico umano A3. Inoltre, con l’intento di selezionare il protocollo di docking molecolare più adatto per la famiglia dei recettori adenosinici, la struttura cristallografica del recettore adenosinico A2A è stata utilizzata per effettuare simulazioni di docking con diversi softwares in parallelo. Successivamente, le conformazioni ottenute dal docking sono state confrontate con la pose cristallografica di ZM241385 per selezionare il protocollo di docking che fosse in grado di riprodurre al meglio questo sistema molecolare e che potesse quindi essere usato per i successivi studi di docking. Sono stati quindi effettuati studi di docking molecolare di vari antagonisti adenosinici sul modello del recettore A3 e sulla struttura cristallografica del recettore A2A, in modo da ricavare informazioni che potessero facilitare il processo di ottimizzazione dei composti. Sono stati infatti analizzati numerosi nuovi composti appartenenti a classi note di antagonisti adenosinici, tra cui composti triazolotriazinici e tirazolotriazolopirimidinici, in modo da suggerire modifiche strutturali in grado di modularne l’affinità nei confronti dei vari sottotipi recettoriali adenosinici, di aumentarne la solubilità o di superarne i punti di instabilità metabolica. Diversi derivati con strutture semplificate, come per esempio composti pirazolopirimidinonici, ftalazinonici e triazolotriazinici, sono stati inoltre proposti come nuovi composti con attività antagonista nei confronti dei recettori adenosinici. Le informazioni ricavate grazie agli studi di docking hanno permesso l’identificazione di caratteristiche strutturali degli antagonisti adenosinici fondamentali per l’interazione con questi recettori. Queste informazioni sono state quindi applicate alla progettazione di derivati fluorescenti per il recettore adenosinico A3, che risultano particolarmente interessanti per il loro potenziale utilizzo in saggi farmacologici. In conclusione, quindi, questo studio sui recettori adenosinici dimostra come l’integrazione di metodologie computazionali con il lavoro sintetico e farmacologico risulta essere una strategia efficace per lo sviluppo di nuovi ligandi dei recettori adenosinici, a potenziale interesse terapeutico, e per il chiarimento di importanti aspetti strutturali riguardanti questa famiglia recettoriale e più in generale tutti i GPCRs.
3
Lee, Hyosung. "DEVELOPMENT OF NOVEL AHR ANTAGONISTS." UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/103.
Full textAbstract:
Aryl hydrocarbon receptor (AHR) is a sensor protein, activated by aromatic chemical species for transcriptionally regulating xenobiotic metabolizing enzymes. AHR is also known to be involved in a variety of pathogenesis such as cancer, diabetes mellitus, cirrhosis, asthma, etc. The AHR signaling induced by xenobiotics has been intensively studied whereas its physiological role in the absence of xenobiotics is poorly understood. Despite a number of ligands of AHR have been reported thus far, further applications are still hampered by the lack of specificity and/or the partially agonistic activity. Thus, a pure AHR antagonist is needed for deciphering the AHR cryptic as well as potential therapeutic agent. The Proteolysis Targeting Chimera (PROTAC) is a bi-functional small molecule containing a ligand and proteolysis inducer. PROTAC recruits the target protein to proteolysis machinery and elicits proteolysis. Thus far, a number of PROTAC have been prepared and demonstrated to effectively induce the degradation of targeted protein in cultured cells, validating PROTAC as a useful research tool. In the present study, PROTACs based on apigenin was prepared and demonstrated to induce the degradation of AHR, providing the proof of concept. To improve activity, a synthetic structure, CH-223191, was optimized for antagonistic activity by positional scanning identifying several AHR antagonists. PROTACs based on the optimal structure were prepared and assessed their biological activity. The products and synthetic scheme described hereby will be helpful for the further understanding on AHR biology as well as for developing therapeutic agents targeting AHR.
4
Pasanisi, F. "Clinical pharmacology of calcium antagonists." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381477.
Full text
5
McClean, Mercedes. "NMDA antagonists as antinociceptive agents." Thesis, University of Bristol, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311427.
Full text
6
Abusara, Osama. "Neuropeptide antagonists for cancer treatment." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/neuropeptide-antagonists-for-cancer-treatment(e2f22b9f-f0a7-432d-89c4-7e65a2c71b69).html.
Full textAbstract:
Small Cell Lung Cancer (SCLC) is an aggressive form of cancer accounting for 25% of lung cancer deaths worldwide. Treatment relies on combination chemotherapy (etoposide and cisplatin or carboplatin) with or without radiation therapy. However, disease relapse and resistance occurs quickly, prompting unmet need for alternative treatment options. One such option is the use of broad-spectrum antagonists, known as Substance P (SP) analogues. Historically, these analogues have not succeeded clinically due to low potency and bioavailability. In this project, novel SP analogues were developed to address these shortfalls. A chemical strategy was designed to synthesise novel short peptides including DMePhe-DTrp-Phe-DTrp-Leu-NH2 (25) as the new lead. Fmoc and Boc D-Trp derivatives with indole nitrogen having substituents (methyl, ethyl, propyl, butyl, pentyl, propargyl, benzyl and tert-prenyl) were made and characterised by 1H and 13C NMR spectroscopy and mass spectrometry (MS). These building blocks were incorporated into the first series of peptides, substituting the D-Trp residue located near the C-terminal of 25, via solid and/or liquid phase procedures. Final products were purified by RP-HPLC to >90% purity and structures verified by MS and/or 1H NMR. Cell viability assays were conducted to evaluate cytotoxicity against two SCLC cell lines: H69 (chemo-naive) and DMS79 (from a patient after treatment). The IC50 values for the D-Trp residue modified peptides were < 5 μM. One of the earliest candidates to emerge from this work was DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2 (33). Subsequently, the most potent peptide was the one bearing D-Trp(N-butyl) (29) with IC50 values of 1.0 μM (H69) and 1.4 μM (DMS79), compared to the lead 25 with IC50 values of 30.7 μM (H69) and 23.0 μM (DMS79). A second series of peptides were produced to optimise 29 by incorporating a D-Trp(N-butyl) residue. The study focused on peptides by (a) modifying the N-terminal D-Trp residue, (b) modifying both D-Trp residues, (c) changing the C-terminal amide to free carboxylic acid, and (d) adding a charged amino acid (arginine) or removing a hydrophobic amino acid (leucine) to additionally aid in solubility. The most potent candidate was found to bear dual D-Trp(N-butyl) residues (35) with IC50 value of 0.6 μM (H69) and 2.3 μM (DMS79). Peptides 29 and 35 were at least 26 times more potent than SP antagonist G (SPG, previously subjected to a Phase I clinical trial), as revealed by in vitro screening in this project. Both sequences induced apoptosis as evident from fluorescence staining. Flow cytometric analysis of 29 with the DMS79 cell line showed that the level of late apoptotic cells rose from 36% at 2 μM to 96% at 6 μM, compared to 25 that exhibited no effect. Efficacy of peptide 33 was separately evaluated in vivo using DMS79 xenografts. A low dose (1.5 mg/kg) was found to reduce tumour growth by ~ 30% (p < 0.05) at day 7, relative to the control group. Higher doses could not be used due to limited aqueous solubility. Furthermore, these peptides were shown to have improved stability. Exposed to neat mouse plasma for 48 hours, 29 and 35 remained intact by 68.5% and 81.0%, respectively, compared to 59.0% for 25 and 35.9% for 33. Complete metabolic stability of 29 and 35 was observed after 3 hours incubation in mouse S9 liver fraction. Aqueous solubility issues were overcome in feasibility studies incorporating 29 into liposomes for future in vivo efficacy testing. Finally, due to the high potency and stability of 29, a liposomal formulation of it may have a profound effect in in vivo efficacy studies against chemo-resistant SCLC.
7
Yocum, David. "Effective use of TNF antagonists." BioMed Central, 2004. http://hdl.handle.net/10150/610348.
Full textAbstract:
Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.
8
Hughes, G. A. "Novel, potent antagonists of capsaicin." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445556/.
Full textAbstract:
The aim of this project was to explore and refine the conformational rationale for the activity of capsazepine (CPZ) as a blocker of the ion channel TRPV1 (transient receptor potential vanilloid type 1), by the synthesis and biological evaluation of further conformational constrained capsaicin analogues. The resolution of the stereoisomers of Af-(4-chlorophenethylthiocarbamoyl)-6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquino-line 29, Af-(4-chlorophenethylthio-carbamoyl)-6,7-dihydroxy-3-methyl-1,2,3,4-tetra-hydroisoquinoline 30 and N-(4-chlorophenethylthiocarbamoyl)-6,7-dihydroxy-1,3-dimethyl-1,2,3,4-tetrahydroiso-quinoline 31 by stereoselective synthetic methodology is described, and some of the more unusual and interesting mechanisms are discussed. The novel asyrnmetric chemistry described includes the separation of the enantiomers of 2-(3,4-dimethoxyphenyl)-l-methylethylamine 38 by crystallisation with the enantiomers of mandelic acid, the use of sodium triacetoxyborohydride in the stereoselective reduction of 6,7-dimethoxy-l,3-dimethyl-3,4-dihydroiso-quinoline 171, to give the cw-diastereomers of 6,7-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline 44, and the novel stereoselective route to the trans-diastereomers of 6,7-dimethoxy-l,3-dimethyl-l,2,3,4-tetrahydroisoquinoline 44 from the enantiomers of 2-(3,4-dimethoxyphenyl)-l-methylethylamine 38 by the Michael addition of A-benzyl-2-(3,4-dimethoxyphenyl)-l-methylethylamine 155 to ethynyl-4-tolylsulfone 150, followed by TFA-mediated cyclisation, single electron reductive desulfonylation and palladium-catalysed hydrogenolysis. The results of investigations into the conformational behaviour of the resolved stereoisomers of 29, 30 and 31 by techniques of NMR spectroscopy and molecular modelling, the evaluation of their biological activity at the rat and human orthologues of the ion channel TRPV1, and the attempted correlation of the two sets of data, with respect to the published conformational rationale for the activity of CPZ, are also described.
9
Sozynski, Jan Maria. "Synthesis of Novel Ethylene Antagonists." Thesis, Curtin University, 2022. http://hdl.handle.net/20.500.11937/89600.
Full textAbstract:
In search of more user-friendly ethylene antagonists, synthesis of water soluble cycloproparenes and [1,2,3]triazolo[1,5-a]pyridines were targeted for this study. A series of precursors to water soluble cycloproparenes were synthesised, however all decomposed in the final reaction. Functionalised analogues of [1,2,3]triazolo[1,5-a]pyridines were prepared and demonstrated some anatgonism of ethylene action in a series of chemical reactivity and preliminary in vivo assays.
10
Arthuso, Fernanda dos Santos. "Adaptação de células CHO secretoras de prolactina humana e seus antagonistas para o crescimento em suspensão." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-20062011-110202/.
Full textAbstract:
O Grupo de Hormônios do Centro de Biotecnologia do IPEN desenvolveu várias linhagens de células de ovário de hamster chinês (CHO) modificadas geneticamente e comprovadamente eficientes na expressão de proteínas heterólogas, dentre elas a prolactina humana (hPRL) e os análogos antagonistas de prolactina (S179D-hPRL e G129R-hPRL). No entanto, todas as linhagens para expressão são cultivadas em monocamadas e dependentes da presença de soro fetal bovino (SFB) no meio de cultivo para um crescimento eficiente. As células em suspensão apresentam um grande interesse industrial-farmacêutico, tanto pela facilidade de cultivo e ampliação de escala, como pela produtividade volumétrica. Desenvolvemos um protocolo para adaptação de células CHO para o crescimento em suspensão e também processos de produção em frascos spinners. Nesse trabalho foi realizada a adaptação das linhagens produtoras de hPRL; S179D-hPRL e G129R-hPRL para o crescimento em suspensão e em meio livre de SFB. Realizamos também a produção em escala laboratorial com as três linhagens adaptadas, assim como a correspondente purificação e caracterização de quatro proteínas heterólogas, incluindo a prolactina humana glicosilada (G-hPRL).The Hormone Group of the Biotechnology Center of IPEN has developed different cells lines of genetically modified chinese hamster ovary cells (CHO) for the expression of heterologus protein like human prolactin (hPRL) and its analogs/antagonists (S179D-hPRL and G129R-hPRL). All cell lines for expression are however cultured in monolayer culture dish and depend on fetal bovine serum (FBS) in the medium for an efficient growth. Cells in suspension show a great industrial-pharmaceutical interest, especially for the cultivation facility and scale enlargement as well as for volumetric productivity. We developed a protocol for adapting CHO cells to suspension growth, in spinner flasks. The adaption of our cell lines producing hPRL; S179D-hPRL and G129R-hPRL to suspension growth and in serum-free medium was obtained. We also carried out laboratory scale production with the three suspension-adapted culture line cells and the corresponding purification and characterization of four heterologous proteins, including glycosylated human prolactin (G-hPRL).
Books on the topic "Antagonists"
1
Godfraind, T., R. Paoletti, S. Govoni, and P. M. Vanhoutte, eds. Calcium Antagonists. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8.
Full text
2
Lydtin, Helmut, and Peter Trenkwalder. Calcium Antagonists. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-74887-5.
Full text
3
Renko, Hal. The antagonists. Wokingham, England: Addison-Wesley, 1985.
Find full text
4
Renko, Hal. The antagonists. Wokingham, Berkshire: Addison-Wesley, 1985.
Find full text
5
Renko, Hal. The antagonists. Wokingham, England: Addison-Wesley, 1985.
Find full text
6
Nayler, W. G. Calcium antagonists. London: Academic, 1988.
Find full text
7
Renko, Hal. The antagonists. Wokingham, Berkshire: Addison-Wesley, 1985.
Find full text
8
Renko, Hal. The antagonists. Wokingham, Berkshire: Addison-Wesley, 1985.
Find full text
9
Germany), MARTa Herford (Herford, ed. OWL4: Gegenspieler = antagonists. Dortmund: Verlag Kettler, 2016.
Find full text
10
Uvnäs, Börje, ed. Histamine and Histamine Antagonists. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-75840-9.
Full textBook chapters on the topic "Antagonists"
1
Landau, Neil. "Antagonists." In The TV Showrunner's Roadmap, 194–210. 2nd ed. New York: Routledge, 2022. http://dx.doi.org/10.4324/9781003041115-9.
Full text
2
Krizanova, Olga, Philippe Lory, and Arnold Schwartz. "Structure-Function Studies of the Voltage-Dependent Calcium Channels." In Calcium Antagonists, 1–8. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_1.
Full text
3
Gaviraghi, G., and T. Godfraind. "New Insight into the Vascular Properties of Lacidipine." In Calcium Antagonists, 65–69. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_10.
Full text
4
Little, W. C., and C. P. Cheng. "Effect of Felodipine on Left Ventricular Performance in Conscious Dogs: Assessment by Left Ventricular Pressure-Volume Analysis." In Calcium Antagonists, 71–76. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_11.
Full text
5
Mancia, Giuseppe. "Lacidipine in the Treatment of Hypertension: Clinical Data." In Calcium Antagonists, 77–85. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_12.
Full text
6
Verdonck, F., F. V. Bielen, L. Ver Donck, and M. Borgers. "Insights in the Cardioprotective Mechanism of the New Drug R56865." In Calcium Antagonists, 87–92. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_13.
Full text
7
Morgan, T., and A. Anderson. "Do the Differences Between Calcium Antagonists Matter When Treating Hypertension?" In Calcium Antagonists, 93–98. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_14.
Full text
8
Boraso, A., A. Cargnoni, A. Maggi, R. Ferrari, and O. Visioli. "Effects of Lacidipine on Ischemic and Reperfused Myocardium." In Calcium Antagonists, 99–106. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_15.
Full text
9
Tulenko, Thomas N., R. Preston Mason, Meng Chen, Hiromi Tasaki, Daniel Rock, and David Stepp. "Atherogenic Activity caused by Excess Membrane Cholesterol in Arterial Smooth Muscle: Role of Calcium Channels." In Calcium Antagonists, 107–15. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_16.
Full text
10
Nayler, Winifred G. "Understanding the Initiating Factors in Atherosclerosis: Implications for Intervention." In Calcium Antagonists, 117–24. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1725-8_17.
Full textConference papers on the topic "Antagonists"
1
Maslak, Diana, A. Orunova, Irina Feklistova, Irina Grineva, Tatyana Skakun, and V. Lomonosova. "Search for isolates of endophytic bacteria-antagonists of phytopathogens." In Scientific International Symposium "Plant Protection – Achievements and Perspectives". Institute of Genetics, Physiology and Plant Protection, Republic of Moldova, 2023. http://dx.doi.org/10.53040/ppap2023.69.
Full textAbstract:
Antagonistic activity of 20 isolates of non-phytopathogenic endophytic bacteria isolated from adult plants of lavender, thyme, St. John's wort and triticale against phytopathogenic microorganisms was studied in laboratory conditions. Nine isolates of endophytic bacteria antagonists of phytopathogens were selected. The ability of selected endophytic antagonist bacteria to protect spring wheat plants of the "Sudarynya" variety from diseases was evaluated in a small-plot experiment under conditions of a natural infectious background. According to the experimental results, endophytic bacteria Tr-2, D-2.1 and L-2 were proposed for research to create new phytoprotective biological preparations.
2
Voitka, D. V., E. K. Yuzefovich, and A. V. Mikhnyuk. "Features of relationship of Trichoderma saprotrophic fungi-antagonists with the phytopathogenic micromycetes." In 2nd International Scientific Conference "Plants and Microbes: the Future of Biotechnology". PLAMIC2020 Organizing committee, 2020. http://dx.doi.org/10.28983/plamic2020.275.
Full textAbstract:
The analysis of the genus Trichoderma saprotrophic fungi-antagonists antagonistic interaction with the phytopathogenic micromycetes is done. The complex mechanism of the antagonistic activity is shown.
3
Bevan, Jane, and S. Heptinstall. "BOW CAN WE INHIBIT 5HT-INDUCED PLATELET AGGREGATION AND WHY SHOULD WE BOTHER?" In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643853.
Full textAbstract:
Platelets are induced to aggregate when 5-hydraxytryptamine (5HT) is added to citrated whole blood and the extent of aggregation can be measured using a Whole Blood Platelet Counter. We have used this method to study a) 5HT-induced platelet aggregation in normal human blood and the effects of 14 5HT receptor antagonists and 2 Ca++-channel blockers, and b) aggregation in blood from patients with peripheral vascular disease (PVD). Previous studies of platelet aggregation in platelet-rich plasma have indicated an increased platelet sensitivity to 5HT in PVD, and a multicentre study of ketanserin (a S2 antagonist) is in progress.5HT induces a transient reversible aggregation in human whole blood which can be prevented by 5HT receptor antagonists. The inhibitory effects of 7 relatively potent antagonists (IC50 7 -41nM, e.g. ketanserin and pizotifen) could not be surmounted by increasing the concentration of 5HT, but the inhibitory effects of 7 less potent antagonists (IC50 0.28 - 53uM, e.g. mepyramine and amitriptyline) could be surmounted by 5-HT. One Ca++-channel blocker (verapamil) inhibited platelet aggregation but another (amlodipine) had very little effect. Verapamil inhibited 5HT-induced aggregation at much lower concentrations (IC50 1.6μM) than those required for aggregation induced by PAF, adrenaline or ADP (IC50 values 32, 33 and >100uM respectively) and the inhibition was insurmountable.5HT-induced platelet aggregation in blood from patients with PVD does not differ qualitatively or quantitatively from aggregation in blood from healthy, age- and sex-matched controls: patients (n = 13), aggregation 30 seconds after adding 5uM 5HT = 55.1% ± 13.3(s.d.); controls (n = 13) aggregation = 48.3% ± 18.9(s.d.). Neither was the platelet aggregation induced by ADP, U46619 or PAF different in patients and controls.We conclude that different 5HT receptor antagonists inhibit 5HT-induced platelet aggregation with different potencies and, apparantly, different mechanisms of action, and that verapamil has a selective effect on 5HT-induced aggregation at relatively low concentrations. Results obtained in PVD do not encourage the use of a 5HT antagonist in this condition.
4
Ribeiro, Fernanda Cristina Poscai, and Everton Lopes Rodrigues. "Integrative review of the use of NMDA antagonists for TBI treatment." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.190.
Full textAbstract:
Introduction: The kinetic energy of TBI generates mechanical deformation, which causes release of glutamate, activating ionotropic receptors, principally NMDA receptors, favoring the flow of Ca++ and Na+ into the cell, producing edema. Then, the neurotoxicity generated by glutamate release can be avoided by NMDA antagonists. Objectives: To define if NMDA antagonists are promising for the treatment of TBI by literature analysis and to verify if there are reports of adverse reactions. Methodology: The review utilized the Scielo and Pubmed databases and the keywords used were: NMDA antagonist, Brain edema and Brain injury. The review contains 5 animal tests and 5 clinical studies. Results: Animal tests: CP-98,133 minimized edema, motor damage and is promising in the treatment of memory dysfunction after TBI. The NPS 1506 reduced edema in 24h, without altering the necrosis significantly. Ketamine decreased the volume of necrosis without altering the edema. HU-211 reduced the edema slightly. Clinical studies: NPS 1506 showed a neuroprotective profile and no serius effects. Traxoprodil decreased the mortality rate by 7%. CP-101.606 improved the patient’s condition, without adverse effects. Conclusion: Although NMDA antagonists demonstrate effectiveness in TBI treatment, more studies about adverse effects and efficiency are still needed. Among those analyzed, traxoprodil, NPS-1506 and CP-101.606 still don’t present serious adverse effects and demonstrate effectiveness, proving promising for new studies.
5
Vasilchenko, N. G., A. V. Gorovtsov, V. A. Chistyakov, and M. S. Mazanko. "BACTERIA OF THE ORDER BACILLALES AS PROMISING ANTAGONISTS OF FUSARIUM PATHOGENS AND THEIR IMPACT ON WINTER WHEAT PLANTS." In INNOVATIVE TECHNOLOGIES IN SCIENCE AND EDUCATION. DSTU-Print, 2020. http://dx.doi.org/10.23947/itno.2020.324-327.
Full textAbstract:
The possibility of using bacteria of the order Bacillales as agents of biological control of phytopathogenic fungi of the genus Fusarium was studied. In the work, 28 soil samples were studied, from which antagonist bacterial strains were isolated. Antagonism was detected by cultivating a pasteurized soil suspension with a culture of the fungus Fusarium graminearum on wort agar. In the course of this work, 1040 antagonist bacterial strains were isolated. Subsequently, the influence of the selected strains of microorganisms on the germination winter wheat seeds and several other morphometric parameters was studied.
6
"IMAGES OF ANTAGONISTS IN THE RELIGIOUS AND MYTHOLOGICAL REPRESENTATIONS OF THE YAKUTS." In Культура, наука, образование: проблемы и перспективы. Нижневартовский государственный университет, 2021. http://dx.doi.org/10.36906/ksp-2021/36.
Full textAbstract:
Yakuts in religious beliefs and heroic epics (olonkho) retain the idea of the highest deities of the cult of ayyy, who act in the image and role of positive heroes together with the heroes of the middle world. The main antagonists are evil spirits (abaaahs) and restless souls (uor). They are also an integral part of Yakut traditionalism. The article presents the traditional classification of antagonistic images in religion and the heroic epic as the main components in the representation of the Yakuts (based on the materials of researchers of the XVIII–XX centuries). In modern society, culture (mass and elite) reflects and forms the idea and worldview of people about a particular image. Accordingly, the study presents images in the mass and elite culture of modern Yakuts, namely in the field of painting, theater and cinema. In the course of our work, we came to the conclusion that the images of the lower mythology (the lower world) are more stable than the images of the upper mythology (the upper world), and, accordingly, are the main actors in the folklore of the people. The traditional images of antagonists in the folklore and religion of the Yakuts appear to us as evil, cold, and also directing misfortunes, diseases, and epidemics at people.
7
Udit, Andrew K. "Engineered virus-like nanoparticle heparin antagonists." In 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2013. http://dx.doi.org/10.1109/embc.2013.6610451.
Full text
8
Santos, Nathalia Lima Schramm dos, William Wallace dos Santos Silva, Geovanna da Silva Campos Conceição, Gabriel Serra Almeida, Jacqueline Oliveira Freitas, Breno Silva Reis, and Lucas Santos Silva. "CGRP antagonists: Perspectives on migraine prophylaxis." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.193.
Full textAbstract:
Introduction: Migraine is a neurovascular disease characterized by headache attacks. Currently there are several preventive therapeutic strategies available, however some patients are not very responsive. Thus, more effective treatments have been researched, like the antagonists of the Calcitonin Gene Related Peptide, the Gepants. Objectives: To evaluate the effectiveness of Gepants in the treatment of migraine. Methods: This is an integrative literature review in the PubMed database, using the descriptors “gepants”, “migraine” and “efficacy”. Only randomized clinical trials conducted from January 2018 to September 2020 were included. Results: Twenty studies were listed, of which 17 use Gepants as a preventive treatment, 2 in acute use and 1 pharmacodynamic study. The Gepants have proved to be a viable option for patients irresponsible to the usual prophylactic regimens. Its significance in reducing migraine and associated symptoms is approximately 50% compared to the placebo group. Evidence of efficacy in the acute crisis is still insufficient. The adverse effects observed had not clinical impact, but more investigations are necessary since most studies exclude people with heart, liver and chronic kidney disease. Another limitation was the use of placebo as a control, not the current prophylactic regimens. Conclusion: This review points to Gepants as a viable option in patients with migraine resistant to the usual regimens. However, there is a need for further studies on adverse effects, comparison with current therapies, drug and pathological interactions.
9
REBER, ANNIE, MARIE-HELENE LEROY, and BERNARD POITEVIN. "VISUO-VESTIBULAR REFLEXES ADJUSTMENT BY GABA ANTAGONISTS." In Proceedings of the International School of Biophysics. WORLD SCIENTIFIC, 1998. http://dx.doi.org/10.1142/9789812816887_0028.
Full text
10
Feklistova, Iryna, Diana Maslak, N. Akiev, T. Skakun, Irina Grineva, and V. Lomonosova. "Search for micromycetes – antagonists of phytopathogenic microorganisms." In Scientific International Symposium "Plant Protection – Achievements and Perspectives". Institute of Genetics, Physiology and Plant Protection, Republic of Moldova, 2023. http://dx.doi.org/10.53040/ppap2023.64.
Full textAbstract:
The antagonistic activity of 11 non-phytopathogenic isolates of microscopic fungi was studied. According to the results of the studies, isolates of microscopic fungi TV, T4 and 6G2, active against phytopathogenic bacteria, inhibiting the growth of mycelium of phytopathogenic fungi, were selected for further research in order to include phytoprotective action in biological preparations. Microscopic fungi TV and T4 were identified as representatives of the genus Trichoderma, micromycete 6G2 was identified as representative of the genus Penicillium, subgenus Eupenicillium.
Reports on the topic "Antagonists"
1
Wilson, Charles, and Edo Chalutz. Biological Control of Postharvest Diseases of Citrus and Deciduous Fruit. United States Department of Agriculture, September 1991. http://dx.doi.org/10.32747/1991.7603518.bard.
Full textAbstract:
The objectives of this research were to develop control measures of postharvest diseases of citrus and deciduous fruits by using naturally-occurring, non-antibiotic-producing antagonists; study the mode of action of effective antagonists and optimize their application methods. Several antagonists were found against a variety of diseases of fruits and vegetables. One particularly effective yeast antagonist (US-7) was chosen for more in-depth studies. This antagonist outcompetes rot pathogens at the wound site for nutrients and space; it is better adapted than the pathogen to extreme environmental conditions such as temperature, humidity and osmotic changes, and is relatively resistant to common postharvest fungicides. Our data suggests that other modes of action may also be involved. These are induction of host resistance by the antagonists or its products, and direct interaction between the antagonists and the pathogen with the possible involvement of an extracellular material and/or cell wall degrading enzymes produced by the antagonist. However, these interactions were not fully elucidated. The antagonistic activity of US-7 and other biocontrol agents isolated, was enhanced by calcium salts. While the mode of action is not known, the addition of these salts had a significant effect both in laboratory experiments and in large-scale tests. Compatibility of the yeast antagonist with present packinghouse treatments and procedures was determined. An integrated control procedure was developed, utilizing the antagonists together with ultra-low dosages of fungicides and activity-enhancing additives. This cooperative research resulted in numerous publications describing the antagonistic agents. their mode of action and possible commercial application. Patents were developed from this research and a commercial company is pursuing the licensing of these patents and the testing of the procedure on a commercial scale. Our research findings have expanded the potential for using non-antibiotic-producing antagonistic microorganisms in the control of postharvest diseases of fruits and vegetables; thus meeting a critical need to find alternatives to the use of synthetic fungicides on food products.
2
Boisclair, Yves R., and Arieh Gertler. Development and Use of Leptin Receptor Antagonists to Increase Appetite and Adaptive Metabolism in Ruminants. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7697120.bard.
Full textAbstract:
Objectives The original project had 2 major objectives: (1) To determine the effects of centrally administered leptin antagonist on appetite and adaptive metabolism in the sheep; (2) To develop and prepare second-generation leptin antagonists combining high binding affinity and prolonged in vivo half-life. Background Periods of suboptimal nutrition or exaggerated metabolic activity demands lead to a state of chronic energy insufficiency. Ruminants remain productive for a surprisingly long period of time under these circumstances by evoking adaptations sparing available energy and nutrients. The mechanism driving these adaptations in ruminant remains unknown, but could involve a reduction in plasma leptin, a hormone acting predominantly in the brain. In laboratory animals, reduced leptin signaling promotes survival during nutritional insufficiency by triggering energy sparing adaptations such as reduced thyroid hormone production and insulin resistance. Our overall hypothesis is that similar adaptations are triggered by reduced leptin signaling in the brain of ruminants. Testing of this hypothesis in ruminants has not been possible due to inability to block the actions of endogenous leptin and access to ruminant models where leptin antagonistic therapy is feasible and effective. Major achievements and conclusions The Israeli team had previously mutated 3 residues in ovine leptin, with no effect on receptor binding. This mutant was renamed ovine leptin antagonist (OLA) because it cannot activate signaling and therefore antagonizes the ability of wild type leptin to activate its receptor. To transform OLA into an effective in vivo antagonist, the Israeli made 2 important technical advances. First, it incorporated an additional mutation into OLA, increasing its binding affinity and thus transforming it into a super ovine leptin antagonist (SOLA). Second, the Israeli team developed a method whereby polyethylene glycol is covalently attached to SOLA (PEG-SOLA) with the goal of extending its half-life in vivo. The US team used OLA and PEG-SOLA in 2 separate animal models. First, OLA was chronically administered directly into the brain of mature sheep via a cannula implanted into the 3rdcerebroventricule. Unexpectedly, OLA had no effect of voluntary feed intake or various indicators of peripheral insulin action but reduced the plasma concentration of thyroid hormones. Second, the US team tested the effect of peripheral PEG-SOLA administration in an energy sensitive, rapidly growing lamb model. PEG-SOLA was administered for 14 consecutive days after birth or for 5 consecutive days before sacrifice on day 40 of life. Plasma PEG-SOLA had a half-life of over 16 h and circulated in 225- to 288-fold excess over endogenous leptin. PEG-SOLA administration reduced plasma thyroid hormones and resulted in a higher fat content in the carcass at slaughter, but had no effects on feed intake, body weight, plasma glucose or insulin. These results show that the team succeeded in developing a leptin antagonist with a long in vivo half-life. Moreover, in vivo results show that reduced leptin signaling promotes energy sparing in ruminants by repressing thyroid hormone production. Scientific and agricultural implications The physiological role of leptin in ruminants has been difficult to resolve because peripheral administration of wild type leptin causes little effects. Our work with leptin antagonists show for the first time in ruminants that reduced leptin signaling induces energy sparing mechanisms involving thyroid hormone production with little effect on peripheral insulin action. Additional work is needed to develop even more potent leptin antagonists, to establish optimal administration protocols and to narrow down phases of the ruminant life cycle when their use will improve productivity.
3
Altstein, Miriam, and Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, August 2013. http://dx.doi.org/10.32747/2013.7593398.bard.
Full textAbstract:
The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.
4
Altstein, Miriam, and Ronald Nachman. Rationally designed insect neuropeptide agonists and antagonists: application for the characterization of the pyrokinin/Pban mechanisms of action in insects. United States Department of Agriculture, October 2006. http://dx.doi.org/10.32747/2006.7587235.bard.
Full textAbstract:
The general objective of this BARD project focused on rationally designed insect neuropeptide (NP) agonists and antagonists, their application for the characterization of the mechanisms of action of the pyrokinin/PBAN (PK-PBAN) family and the development of biostable, bioavailable versions that can provide the basis for development of novel, environmentally-friendly pest insect control agents. The specific objectives of the study, as originally proposed, were to: (i) Test stimulatory potencies of rationally designed backbone cyclic (BBC) peptides on pheromonotropic, melanotropic, myotropic and pupariation activities; (ii) Test the inhibitory potencies of the BBC compounds on the above activities evoked either by synthetic peptides (PBAN, LPK, myotropin and pheromonotropin) or by the natural endogenous mechanism; (iii) Determine the bioavailability of the most potent BBC compounds that will be found in (ii); (iv) Design, synthesize and examine novel PK/PBAN analogs with enhanced bioavailability and receptor binding; (v) Design and synthesize ‘magic bullet’ analogs and examine their ability to selectively kill cells expressing the PK/PBAN receptor. To achieve these goals the agonistic and antagonistic activities/properties of rationally designed linear and BBC neuropeptide (NP) were thoroughly studied and the information obtained was further used for the design and synthesis of improved compounds toward the design of an insecticide prototype. The study revealed important information on the structure activity relationship (SAR) of agonistic/antagonistic peptides, including definitive identification of the orientation of the Pro residue as trans for agonist activity in 4 PK/PBANbioassays (pheromonotropic, pupariation, melanotropic, & hindgut contractile) and a PK-related CAP₂b bioassay (diuretic); indications that led to the identification of a novel scaffold to develop biostbiostable, bioavailable peptidomimetic PK/PBANagonists/antagonists. The work led to the development of an arsenal of PK/PBAN antagonists with a variety of selectivity profiles; whether between different PKbioassays, or within the same bioassay between different natural elicitors. Examples include selective and non-selective BBC and novel amphiphilic PK pheromonotropic and melanotropic antagonists some of which are capable of penetrating the moth cuticle in efficacious quantities. One of the latter analog group demonstrated unprecedented versatility in its ability to antagonize a broad spectrum of pheromonotropic elicitors. A novel, transPro mimetic motif was proposed & used to develop a strong, selective PK agonist of the melanotropic bioassay in moths. The first antagonist (pure) of PK-related CAP₂b diuresis in flies was developed using a cisPro mimetic motif; an indication that while a transPro orientation is associated with receptor agonism, a cisPro orientation is linked with an antagonist interaction. A novel, biostablePK analog, incorporating β-amino acids at key peptidase-susceptible sites, exhibited in vivo pheromonotropic activity that by far exceeded that of PBAN when applied topically. Direct analysis of neural tissue by state-of-the-art MALDI-TOF/TOF mass spectrometry was used to identify specific PK/PK-related peptides native to eight arthropod pest species [house (M. domestica), stable (S. calcitrans), horn (H. irritans) & flesh (N. bullata) flies; Southern cattle fever tick (B. microplus), European tick (I. ricinus), yellow fever mosquito (A. aegypti), & Southern Green Stink Bug (N. viridula)]; including the unprecedented identification of mass-identical Leu/Ile residues and the first identification of NPs from a tick or the CNS of Hemiptera. Evidence was obtained for the selection of Neb-PK-2 as the primary pupariation factor of the flesh fly (N. bullata) among native PK/PK-related candidates. The peptidomic techniques were also used to map the location of PK/PK-related NP in the nervous system of the model fly D. melanogaster. Knowledge of specific PK sequences can aid in the future design of species specific (or non-specific) NP agonists/antagonists. In addition, the study led to the first cloning of a PK/PBAN receptor from insect larvae (S. littoralis), providing the basis for SAR analysis for the future design of 2ⁿᵈgeneration selective and/or nonselective agonists/antagonists. Development of a microplate ligand binding assay using the PK/PBAN pheromone gland receptor was also carried out. The assay will enable screening, including high throughput, of various libraries (chemical, molecular & natural product) for the discovery of receptor specific agonists/antagonists. In summary, the body of work achieves several key milestones and brings us significantly closer to the development of novel, environmentally friendly pest insect management agents based on insect PK/PBANNPs capable of disrupting critical NP-regulated functions.
5
Tracy, Michael. Improved Muscarinic Antagonists as Anticholinesterase Antidotes. Fort Belvoir, VA: Defense Technical Information Center, March 1991. http://dx.doi.org/10.21236/ada242697.
Full text
6
Schmidt, Jakob. Mass-Screening of Curarimimetic Neurotoxin Antagonists. Fort Belvoir, VA: Defense Technical Information Center, March 1990. http://dx.doi.org/10.21236/ada222729.
Full text
7
Tracy, Michael. Improved Muscarinic Antagonists as Anticholinesterase Antidotes. Fort Belvoir, VA: Defense Technical Information Center, February 1990. http://dx.doi.org/10.21236/ada223689.
Full text
8
Kao, C. Y. Site-Specific Antagonists to Tetrodotoxin and Saxitoxin. Fort Belvoir, VA: Defense Technical Information Center, May 1988. http://dx.doi.org/10.21236/adb124671.
Full text
9
Kao, C. Y. Site-Specific Antagonists to Tetrodotoxin and Saxitoxin. Fort Belvoir, VA: Defense Technical Information Center, May 1990. http://dx.doi.org/10.21236/adb145447.
Full text
10
Chalutz, Edo, Michael Wisniewski, Samir Droby, Yael Eilam, and Ilan Chet. Mode of Action of Yeast Biocontrol Agents of Postharvest Diseases of Fruits. United States Department of Agriculture, June 1996. http://dx.doi.org/10.32747/1996.7613025.bard.
Full textAbstract:
In a previous BARD-supported study, three of the investigators of this research were involved in a study on biological control of postharvest diseases of citrus and deciduous fruits. Several naturally occurring, non-antibiotic producing yeast antagonists were identified. Application of some of these antagonists resulted in very high levels of biocontrol under laboratory conditions but lower efficacy in semi-commercial tests. It was felt that the lack of knowledge on the mode of action of the biocontrol agents was limiting their efficient use. The current study was aimed at narrowing this gap in our knowledge. Two specific objectives were outlined: to study the mechanism by which calcium salts enhance biocontrol activity and to determine the role, if any, of the yeast extracellular materials and/or enzymes which degrade fungal cell walls during the interaction between the antagonists, the pathogen and the host. CaCl2 but not MgCl2, inhibited spore germination, and germ-tube elongation of Botrytis cinerea, Penicillium expansum and P. digitatum in culture. It also inhibited the pectinolytic activity of the pathogens. Biocontrol of apple decay by isolate 182 of Candida oleophila, an effective biocontrol agent, was enhanced by the addition of CaCl2 whereas there was no effect on the biocontrol activity of isolate 247 of this yeast. Similarly, CaCl2 enhanced efficacy of the US-7 isolate of Pichia guilliermondii in reducing infection of P. digitatum in citrus fruit. CaCl2 by itself also reduced the infection of peel wounds and stimulated ethylene production by grapefruit peel. This antagonist exhibited a very high ability to maintain cytosolic Ca2+ homeostasis when exposed to high CaCl2 concentrations. It is postulated, therefore, that enhanced biocontrol activity by calcium is the result of direct inhibition of the pathogen by calcium ions on spore germination and metabolism and indirectly due to the ability of the biocontrol agent to maintain normal metabolism in the presence of high levels of calcium. The extracellular materials produced by P. guilliermondii in culture and on the fruit inhibited, at low concentrations, the pathogen in culture and reduced percent infection of the fruit. The direct inhibition of the pathogen by these materials may thus be involved in the mode of action of the antagonist. This study contributed to our knowledge on the action of calcium salts and the yeast antagonist extracellular materials on biocontrol activity and will contribute to a more efficient use of this technology in the control of postharvest diseases of fruits.