| 7452679 |
Synthesis and some pharmacological properties of 8-L-tryptophanoxytocin |
10.1021/jm00185a025. |
J Med Chem |
Synthesis and some pharmacological properties of 8-L-tryptophanoxytocin
Abstract
- Condensation of (tert-butyloxycarbonyl)tocinoic acid with L-prolyl-L-tryptophylglycinamide produced the Boc derivative of a nonapeptide (disulfide) which on deprotection afforded 8-L-tryptophanoxytocin. In assays on the rat uterus in vitro and in vivo the new analogue acts as both an agonist and an antagonist. The duration of both actions is prolonged.
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| 7470459 |
Synthetic cation transport peptides: calcium transport across phospholipid membranes |
10.1021/bi00567a038. |
Biochemistry |
Synthetic cation transport peptides: calcium transport across phospholipid membranes
Abstract
- Molecular aspects of peptide-mediated calcium transport are examined through the study of the cation transport properties of a series of synthetic cyclic octapeptides. These peptides, of general structure cycloGlu(OR1)-Sar-Gly-(N-R2)Gly2 (R1 = H or benzyl ester; R2 = cyclohexyl, n-hexyl, or n-decyl) (and an Asp analogue), contain central binding cavities of geometry and dimensions similar to calcium-binding sites in proteins. Transport in Pressman cells ("thick liquid membranes") demonstrated the ionophorous activity of the synthetic peptides; among physiologically abundant cations, the order of selectivity was Ca2+ greater than Na+, K+ much greater than Mg2+. Cation competition studies further showed that cycloGlu(OBz)-Sar-Gly-(N-cyclohexyl)Gly2 (CYCLEX-2E) is essentially a calcium-specific transport peptide whenever calcium is present. When the CYCLEX-2E peptide was added to a suspension of 45Ca2+-loaded sonicated phosphatidylcholine (PC) vesicles in a dialysis sac, the vesicles were completely emptied of internal calcium. Controls using 14Csucrose established that CYCLEX-2E caused no nonspecific membrane damage. Calcium efflux experiments using several salts of calcium (including 36C1-, 14Cacetate, 14Csuccinate, and 35SO4(2-)) suggested that these anions do not specifically accompany the Ca2+-peptide active transporting species across the phospholipid membrane. However, when 45Ca2+-loaded PC vesicles were suspended in mental-free buffer and treated with CYCLEX-2E peptide, calcium efflux did not occur until calcium or sodium chloride was added to the external medium.
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| 7479320 |
Behavioral effects of the cyclic cholecystokinin peptide analogue JMV-320 |
10.1016/0196-9781(94)00214-q. |
Peptides |
Behavioral effects of the cyclic cholecystokinin peptide analogue JMV-320
Abstract
- The in vivo effects of JMV-320 (a highly selective CCKB receptor ligand) and of CCK-4 on exploratory activity and memory in rats were compared. JMV-320 and CCK-4 did not modulate exploratory activity in an open field test but decreased it in an elevated plus-maze. CCK-4 (50 micrograms/kg) impaired passive avoidance response 3 h after training and JMV-320 (1 and 10 micrograms/kg) decreased active avoidance response 24 h after training. The behavioral effects of JMV-320 resemble the effects of CCK-4 and suggest that in vivo JMV-320 acts as a CCKB receptor agonist.
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| 7486919 |
Aerosol and parenteral pneumocandins are effective in a rat model of pulmonary aspergillosis |
10.1128/AAC.39.8.1784. |
Antimicrob Agents Chemother |
Aerosol and parenteral pneumocandins are effective in a rat model of pulmonary aspergillosis
Abstract
- The pneumocandins are semisynthetic analogs of echinocandin-like compounds that have shown efficacy in animal models of systemic candidiasis, disseminated aspergillosis, and pneumocystis pneumonia. However, the most common form of Aspergillus infection in susceptible patients is pulmonary aspergillosis, which was not directly tested in the mouse models used in the past. We have evaluated three pneumocandins, L-693,989, L-731,373, and L-733,560, in a rat model of pulmonary aspergillosis. Male Sprague-Dawley rats were treated for 2 weeks with cortisone and tetracycline and fed a low-protein diet before being inoculated via the trachea with 10(6) conidia of Aspergillus fumigatus H11-20. In the absence of drug treatment, the animals developed a progressive, rapidly fatal bronchopneumonia. All three pneumocandins at doses of 5 mg/kg (intraperitoneally i.p. every 12 h q12h) were effective in delaying mortality in this model. Survival at day 7 postinfection was 20% among controls (n = 10 for all groups), while it was 60, 80, and 90% in groups that were treated with L-693,989, L-731,373, and L-733,560, respectively. In another trial, survival at day 7 postinfection was 25% among controls (n = 8 for all groups); it was 87.5% in a group treated with amphotericin B (0.5 mg/kg i.p. q12h) and was 100% in a group treated with L-733,560 (0.625 mg/kg i.p. q12h). In a separate trial, aerosol L-693,989 administered 2 h before infection (5 mg/kg) delayed mortality. Eight of the 10 animals treated with aerosol L-693,989 survived for 7 days, whereas only 2 of 10 control animals survived. We conclude that the pneumocandins we tested were highly effective in an animal model of pulmonary aspergillosis.
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| 7488001 |
The synthetic Tyr5,12,Lys7-polyphemusin II peptide (T22) binds to the CD4 cell surface molecule |
10.1006/bbrc.1995.2510. |
Biochem Biophys Res Commun |
The synthetic Tyr5,12,Lys7-polyphemusin II peptide (T22) binds to the CD4 cell surface molecule
Abstract
- The Tyr5,12,Lys7-polyphemusin II peptide (T22) inhibits HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that the T22 peptide binds to the CD4 molecule in affinity columns. We also find that antiserum to CD4 inhibits cell attachment to T22. Further CD4+ transfected cells attach to T22 while their parental cells which do not express CD4 do not attach to T22. These data demonstrate that T22 binds to the CD4 molecule and supports the hypothesis that T22 inhibits HIV-1 replication by binding to the cell surface CD4 molecule and inhibiting uptake of the virus.
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| 7489242 |
A monoclonal antibody that recognizes the GPIIb/IIIa antagonist DMP 728. Reversal of the effects of DMP 728 on platelet aggregation and bleeding time in the dog |
10.1161/01.atv.15.12.2195. |
Arterioscler Thromb Vasc Biol |
A monoclonal antibody that recognizes the GPIIb/IIIa antagonist DMP 728. Reversal of the effects of DMP 728 on platelet aggregation and bleeding time in the dog
Abstract
- Since hemorrhagic events represent a major safety concern associated with the use of new antithrombotic therapies such as glycoprotein (GP) IIb/IIIa receptor blockade, we evaluated the ability of a monoclonal antibody recognizing DMP 728 (cyclic D-2-aminobutyryl-N2-methyl-L-argininyl-glycyl-L-aspartyl-3- aminomethyl-benzoic acid methanesulfonic acid salt), a potent GPIIb/IIIa receptor antagonist, to reverse the pharmacological actions of DMP 728 in the dog. DC11 was chosen for in vivo evaluation based on its ability to inhibit the binding of 3HDMP 728 to activated platelets and to attenuate the inhibition of ADP-induced aggregation on platelet-rich plasma ex vivo by DMP 728. After anesthesia mongrel dogs were given DMP 728 (20 micrograms/kg body wt IV) infused into the femoral vein, bleeding times were determined using a Simplate device from incisions on the backside of the tongue, and platelet aggregation was determined ex vivo. Nearly complete inhibition of platelet aggregation was observed for the dogs treated with DMP 728 (20 ug/kg IV) for up to 210 minutes, and bleeding times were prolonged > 15 minutes for 2 hours and remained elevated for more than 4 hours. DC11 (0.2 or 1.0 mg/kg body wt IV) given to dogs 10 minutes after DMP 728 resulted in 50% attenuation of the effect of DMP 728 on aggregation at 3 hours. Approximately 34% inhibition of the DMP 728-mediated bleeding time was achieved at 1 hour with the 0.2 mg/kg dose, whereas approximately 50% inhibition of the bleeding time was observed for the 1 mg/kg dose at 1 hour.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 7490214 |
Bacillopeptins, new cyclic lipopeptide antibiotics from Bacillus subtilis FR-2 |
10.7164/antibiotics.48.1095. |
J Antibiot (Tokyo) |
Bacillopeptins, new cyclic lipopeptide antibiotics from Bacillus subtilis FR-2
Abstract
- Bacilopeptins, new iturin-group antifungal antibiotics, were isolated from the culture broth of Bacillus subtilis FR-2 obtained from the rhizosphere of garlic suffering from the basal rot caused by Fusarium oxysporum. Their structures were elucidated to be cyclic lipopeptides similar to bacillomycin L by NMR and mass spectral studies coupled with amino acid analysis. The absolute configuration of each amino acid residue was determined by chiral HPLC.
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| 7490217 |
Structure of new cyclic depsipeptides, Bu-2841-08 and -10 |
10.7164/antibiotics.48.1115. |
J Antibiot (Tokyo) |
Structure of new cyclic depsipeptides, Bu-2841-08 and -10
Abstract
- The structures of new antibiotics, Bu-2841-08 and -10, have been determined. They are cyclic depsipeptides and the sequence of amino acid residues was established by mass spectral analysis of the hydrolyzed linear peptide and NMR spectral analysis of the parent cyclic peptides.
|
| 7498547 |
cDNA sequences of three sheep myeloid cathelicidins |
10.1016/0014-5793(95)01285-3. |
FEBS Lett |
cDNA sequences of three sheep myeloid cathelicidins
Abstract
- Several myeloid antimicrobial peptide precursors have been shown to consist of a N-terminal proregion similar to a protein named cathelin and a structurally varied C-terminal antimicrobial domain. Proteins with these features have been named cathelicidins. In this paper we report the cDNA sequences of three ovine cathelicidins of 155, 160 and 190 residues, respectively, with cationic C-terminal sequences corresponding to putative antimicrobial domains. These are structurally varied and include a Cys-rich sequence of 12 residues, which is similar to the bovine antimicrobial cyclic dodecapeptide, a novel 29 residue sequence named SMAP-29 with a possible alpha-helical conformation, and a 60 residue sequence named Bac7.5, which appears to be a new member of the Pro- and Arg-rich group of mammalian antimicrobial peptides.
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| 7500362 |
Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate |
10.1006/jmbi.1995.0667. |
J Mol Biol |
Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate
Abstract
- Protein phosphatase 1 (PP1) is a serine/threonine protein phosphatase that is essential in regulating diverse cellular processes. Here we report the crystal structure of the catalytic subunit of human PP1 gamma 1 and its complex with tungstate at 2.5 A resolution. The anomalous scattering from tungstate was used in a multiple wavelength anomalous dispersion experiment to derive crystallographic phase information. The protein adopts a single domain with a novel fold, distinct from that of the protein tyrosine phosphatases. A di-nuclear ion centre consisting of Mn2+ and Fe2+ is situated at the catalytic site that binds the phosphate moiety of the substrate. Proton-induced X-ray emission spectroscopy was used to identify the nature of the ions bound to the enzyme. The structural data indicate that dephosphorylation is catalysed in a single step by a metal-activated water molecule. This contrasts with other phosphatases, including protein tyrosine phosphatases, acid and alkaline phosphatases which form phosphoryl-enzyme intermediates. The structure of PP1 provides insight into the molecular mechanism for substrate recognition, enzyme regulation and inhibition of this enzyme by toxins and tumour promoters and a basis for understanding the expanding family of related phosphatases which include PP2A and PP2B (calcineurin).
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| 7504215 |
Comparison of the effects of (+/-) CP 96,345 and L-668,169 on neurokinin receptor mediated responses in rat and guinea-pig isolated tissues |
10.1016/0143-4179(93)90099-v. |
Neuropeptides |
Comparison of the effects of (+/-) CP 96,345 and L-668,169 on neurokinin receptor mediated responses in rat and guinea-pig isolated tissues
Abstract
- The effects of (+/-) CP 96,345 and L-668,169 on NK1-, NK2- and NK3-receptor mediated contractile responses were compared in guinea-pig and rat isolated smooth muscle tissues. Both (+/-) CP 96,345 and L-668,169 inhibited NK1-mediated responses in guinea-pig ileum (pA2 = 9.3 and 6.4 respectively) but not in rat bladder (pKB = < 6 and < 5.5 respectively) consistent with species differences in NK1-receptor pharmacology. Both compounds showed some selectivity in inhibiting NK1-receptor evoked responses in guinea-pig ileum compared to their inhibitory effects on NK2-receptor mediated responses in guinea-pig bladder and rat ileum and NK3-mediated responses in guinea-pig ileum and rat portal vein.
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| 7509257 |
Antiplatelet efficacy and specificity of DMP728, a novel platelet GPIIb/IIIa receptor antagonist |
10.1159/000175994. |
Cardiology |
Antiplatelet efficacy and specificity of DMP728, a novel platelet GPIIb/IIIa receptor antagonist
Abstract
- The present study was undertaken to define the platelet GPIIb/IIIa affinity and specificity of DMP728, the cyclic (D-2-aminobutyrate-N-methyl-L-arginyl-glycyl-L-aspartyl)-3-aminomethyl- benzoic acid methane sulfonate. DMP728 demonstrated similar potency (IC50 = 0.046 +/- 0.002 microM) in inhibiting human platelet aggregation induced by various agonists or combination of agonists as assessed either by light transmittance aggregometry or impedance techniques. Similarly, DMP728 inhibited (IC50 = 2.3 +/- 0.8 nM) with equipotency in inhibiting 125I-fibrinogen binding to human gel-purified platelets regardless of the agonist used. In purified human GPIIb/IIIa ELISA, DMP728 demonstrated a competitive high affinity binding (Ki = 0.4 nM). Additionally, a high binding affinity (Kd = 0.1 nM) of 3H-DMP728 was demonstrated in human platelets. Furthermore, a platelet deaggregatory efficacy was shown. DMP728 demonstrated a high degree of specificity for platelet GPIIb/IIIa (alpha 2/beta 3) as compared to other integrins on endothelial cells (vitronectin receptors), platelets GPIb/1X, alpha v/beta 3, and other integrins on leukocytes or nonintegrin-related systems. In conclusion, DMP728 is a novel antiplatelet agent with high affinity and specificity for platelet GPIIb/IIIa.
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| 7509748 |
Differences in the effects of tachykinin NK1 receptor antagonists: neuronal versus smooth muscle tissues |
10.1016/0014-2999(93)90629-v. |
Eur J Pharmacol |
Differences in the effects of tachykinin NK1 receptor antagonists: neuronal versus smooth muscle tissues
Abstract
- The effects of three tachykinin NK1 receptor antagonists (L-668,169, (+/-)-RP 67580, and (+/-)-CP 96.345) were examined for their ability to antagonise responses evoked by substance P O-methyl ester (a selective NK1 receptor agonist) in isolated neuronal tissue (rat superior cervical ganglia and guinea-pig locus coeruleus) and smooth muscle tissues (rat urinary bladder and guinea-pig ileum longitudinal muscle/myenteric plexus). (+/-)-RP 67580 was similarly effective in antagonising responses in both rat superior cervical ganglia and urinary bladder (estimated pKa value = 7.4 for both tissues); however, (+/-)-CP 96,345 was 50-fold less effective in antagonising responses in guinea-pig locus coeruleus than in ileum longitudinal muscle/myenteric plexus (estimated pKa values = 7.6 and 9.3 respectively). It is suggested that the differential effects of (+/-)-CP 96,345 may reflect the existence of a population of NK1 receptors within guinea-pig locus coeruleus that are less sensitive to the effects of this NK1 receptor antagonist.
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| 7511473 |
Vapreotide, a new somatostatin analogue in the palliative management of obstructive ileus in advanced cancer |
10.1007/BF00326640. |
Support Care Cancer |
Vapreotide, a new somatostatin analogue in the palliative management of obstructive ileus in advanced cancer
Abstract
- Obstructive ileus is not common, but is a very distressing syndrome in a palliative care unit. The case of a 86-year-old woman with obstructive ileus due to advanced pancreatic cancer is presented. Successful management was made possible by a new somatostatin analogue (Vapreotide), administered i.m. at weekly intervals. Vapreotide was found to reduce nausea and vomiting considerably, by inhibiting the release and action of gastrointestinal hormones and the secretory and motor functions of stomach and intestines. The role of somatostatin analogues in the management of obstructive ileus in advanced cancer is discussed.
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| 7516023 |
Antithrombotic effects of DMP 728, a platelet GPIIb/IIIa receptor antagonist, in a canine model of arterial thrombosis |
10.1097/00005344-199404000-00025. |
J Cardiovasc Pharmacol |
Antithrombotic effects of DMP 728, a platelet GPIIb/IIIa receptor antagonist, in a canine model of arterial thrombosis
Abstract
- The platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa, fibrinogen receptor) represents the final common pathway for platelet aggregation. Inhibition of GPIIb/IIIa with antibodies or peptides containing the RGD sequence has been reported to prevent arterial thrombosis. We examined DMP 728 (cyclicD-2-amino-butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3-(a min o- methyl-benzoic acid, methanesulfonic acid salt, a cyclic peptidomimetic, GPIIb/IIIa receptor antagonist, for prevention of thrombosis and rethrombosis in a canine model of carotid artery thrombosis. Dogs were anesthetized, and both carotid arteries were instrumented with an electrode, a flow probe, and a stenosis. A 300-microA current was applied to the intimal surface in the right carotid artery (RCA, control) through the electrode; time to occlusive thrombus formation and thrombus mass was noted. The RCA served as the control vessel; the left carotid artery (LCA) served as the test vessel after DMP 728 administration (0.1 or 1. mg/kg, intravenously, i.v.). As compared with controls, occlusive thrombus formation was reduced by both doses of DMP 728 (control 100% n = 12; 0.1 mg/kg i.v. 17%, p < 0.05, n = 6; 1.0 mg/kg i.v. 0%, p < 0.05, n = 6), time to occlusion was increased (p < 0.05), and thrombus weight was reduced (p < 0.05). Ex vivo platelet aggregation was inhibited in all groups. In a second group of animals, a carotid artery thrombus was formed and lysed with anisoylated plasminogen activator complex (APSAC; 0.05 U/kg intraarterially, i.a.) with or without DMP 728.(ABSTRACT TRUNCATED AT 250 WORDS)
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