| 1762065 |
Distribution and analgesia of 3HD-Pen2, D-Pen5enkephalin and two halogenated analogs after intravenous administration |
None |
J Pharmacol Exp Ther |
Distribution and analgesia of 3HD-Pen2, D-Pen5enkephalin and two halogenated analogs after intravenous administration
Abstract
- To improve pharmacological characteristics of the delta-selective, cyclic peptide D-Pen2, D-Pen5enkephalin (DPDPE), modification by halogenation at the Phe4 residue was undertaken. The present study was to determine the extent 3HDPDPE, 3Hp-Cl-Phe4DPDPE and p-125IPhe4DPDPE crosses the blood-brain barrier, elicits analgesia and to characterize selective organ distribution and stability after i.v. administration. A significantly greater percentage of total 3Hp-Cl-Phe4DPDPE reached the brain after 10, 20 and 40 min as compared to 3HDPDPE and both peptides were significantly displaced by pretreatment with naloxone or naltrindole. The amount of 3HDPDPE detected in the brain was greater than that of p-125IPhe4DPDPE. Distribution results revealed large amounts of the administered peptides were sequestered rapidly in the gall bladder and secreted into the small intestine. Hot-plate antinociception tests 5 min after i.v. administration (30 and 60 mg/kg) revealed p-Cl-Phe4DPDPE to elicit a much greater analgesic effect as compared to DPDPE or p-125IPhe4DPDPE. These results provide evidence that p-Cl-Phe4DPDPE has a greater apparent distribution to the brain and has a greater effect on the antinociception threshold as tested on the hot-plate than DPDPE or p-125IPhe4DPDPE. Stability of unlabeled and tritiated DPDPE and p-Cl-Phe4DPDPE was determined both in vitro and in vivo; both unlabeled and tritiated DPDPE and p-Cl-Phe4DPDPE remain intact.
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| 1764727 |
Distribution of actin-filament bundles in myoid cells, Sertoli cells, and tunica albuginea of rat and mouse testes |
10.1007/BF00318185. |
Cell Tissue Res |
Distribution of actin-filament bundles in myoid cells, Sertoli cells, and tunica albuginea of rat and mouse testes
Abstract
- Frozen sections of the rat and mouse testes were stained with either FITC-phalloidin or NBD-phallacidin and viewed with conventional fluorescence and confocal laser microscopes in order to demonstrate the arrangement of actin-filament bundles in myoid cells, Sertoli cells and tunica albuginea. Myoid cells are rich in actin-filament bundles crossing at right angles. These bundles running in different directions can also be visualized by means of electron microscopy. Nerve fibers occur in the vicinity of myoid cells, suggesting a neural control of the cell. At Sertoli cell junctions actin filaments occur at the circumference of the cell, where they show a honeycomb pattern. The ratio of the number of Sertoli cells per myoid cell can be calculated by means of confocal microscopy; this technique may provide a new parameter for determining spermatogenic activity. In the tunica albuginea of the juvenile mouse testis, actin filaments are arranged in an alternate fashion.
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| 1779878 |
Studies on the antifungal antibiotics: bacillomycin D and bacillomycin D methylester |
None |
Microbios |
Studies on the antifungal antibiotics: bacillomycin D and bacillomycin D methylester
Abstract
- Bacillomycin D, an antifungal compound of Bacillus subtilis, was produced during the stationary phase of growth when all the glucose of the medium was exhausted and the pH reached about 8. In addition to bacillomycin D, bacillomycin D methylester was characterized by its antifungal properties and its haemolytic activity.
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| 1790297 |
beta-Alanyl-beta-alanine in cyclic beta-turned peptides |
10.1002/bip.360311006. |
Biopolymers |
beta-Alanyl-beta-alanine in cyclic beta-turned peptides
Abstract
- In the present paper we describe the synthesis, purification, and single crystal x-ray analysis of the cyclic pentapeptide cyclo-(L-Pro-L-Pro-L-Phe-beta-Ala-beta-Ala). The peptide was synthesized by classical solution methods and the cyclization of the free pentapeptide was accomplished in good yields in diluted methylene-chloride solution using N,N-dicyclohexylcarbodiimide. The compound crystallizes in the monoclinic space group P21 from hot water with five solvent molecules. The Pro1-Pro2 peptide bond is cis and the molecular conformation is stabilized by an intramolecular hydrogen bond between the CO group of the beta-Ala5 and the NH of the Phe3 residue. The Pro1-Pro2 segment occupies the relative positions 2 and 3 of a type VIa beta-turn, while the L-phenylalanyl-beta-alanyl-beta-alanine segment is incorporated in a C13-like ring structure. The crystal packing is characterized by a network of 11 intermolecular hydrogen bonds involving all the remaining CO, NH, and the water molecules.
|
| 1793802 |
Microcystins from Anabaena flos-aquae NRC 525-17 |
10.1021/tx00023a008. |
Chem Res Toxicol |
Microcystins from Anabaena flos-aquae NRC 525-17
Abstract
- Anabaena flos-aquae NRC 525-17 produces a very potent neurotoxin, anatoxin-a(s). During isolation of the neurotoxin, we found that the strain contains four other toxic compounds which show strong hepatotoxicity. The four toxins, toxins 1, 1', 2, and 3, were successfully purified. Toxin 2, one of major toxins, was identified as 3-desmethylmicrocystin LR (1) by comparison of spectral data of the known compound. Since the three other toxins contain an unknown amino acid, GC/MS was applied and it revealed the presence of homotyrosine in toxins 1 (2) and 1' (3). Only a partial structure was obtained for toxin 3 due to the small amount present in the cells."
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| 1797443 |
Conformational analysis of n-demethyl-Tyr(OCH3)-3RA-VII, conformationally restricted model approach |
10.1248/cpb.39.2161. |
Chem Pharm Bull (Tokyo) |
Conformational analysis of n-demethyl-Tyr(OCH3)-3RA-VII, conformationally restricted model approach
Abstract
|
| 1804412 |
Determination of the amino acid sequence of cystine-containing peptides by tandem mass spectrometry |
10.1002/rcm.1290050404. |
Rapid Commun Mass Spectrom |
Determination of the amino acid sequence of cystine-containing peptides by tandem mass spectrometry
Abstract
- A method has been developed for the determination of the amino-acid sequence of a cyclic peptide containing cystine. It is based on the reduction of the peptide in a reductive matrix prior to ionization by fast-atom bombardment. The amino-acid sequence of the resulting linear peptide is then determined by tandem mass spectrometry from the spectrum produced by the collision-induced decomposition of the M + H+ ion of the peptide.
|
| 1816575 |
Long-lasting dopamine receptor up-regulation in amphetamine-treated rats following amphetamine neurotoxicity |
10.1016/0091-3057(91)90101-7. |
Pharmacol Biochem Behav |
Long-lasting dopamine receptor up-regulation in amphetamine-treated rats following amphetamine neurotoxicity
Abstract
- Amphetamine (A) (9.2 mg/kg, IP), in combination with iprindole (I) (10.0 mg/kg, IP), caused long-lasting dopamine (DA) depletions in striatum (-49%, 4 weeks) but not in nucleus accumbens following one A/I injection. Striatal DA had recovered by 4 months. DA receptors (DAr) were up-regulated: 1) behavioral responses to a DA receptor agonist (apomorphine) were significantly elevated. These included apomorphine-induced locomotor activity (+103% and +160%, on weeks 3 and 10) and apomorphine-induced stereotypy (day 10). 2) Bmax for 3Hspiroperidol binding to striatal D2 DAr (12 weeks) increased (+53%, week 12). Injection of the DAr neuromodulator cyclo(leucyl-glycyl) (8 mg/kg/day x 4 days, SC) reversed the Bmax increase. Thus toxicity (DA depletion) following high-dose amphetamine appears to induce compensatory changes in DAr. This DAr upregulation may explain the lack of abnormal movements despite enduring DA depletion. Additionally, the A/I paradigm as an animal model of long-lasting DAr up-regulation, could be used to screen neuromodulatory agents, like CLG, that might treat disorders (e.g., tardive dyskinesia and schizophrenia) thought to involve up-regulated DAr.
|
| 1818205 |
Yeast glucan of Pneumocystis carinii cyst wall: an excellent target for chemotherapy |
None |
J Protozool |
Yeast glucan of Pneumocystis carinii cyst wall: an excellent target for chemotherapy
Abstract
- Pneumocystis pneumonia is the most serious opportunistic infection in immunocompromised patients, particularly those with AIDS. Approved therapy is limited to pentamidine and inhibitors of folic acid synthesis, but these drugs show a high rate of adverse reactions in AIDS patients emphasizing the urgent need for additional effective therapies. Progress has, however, been hindered by lack of knowledge about this parasite's cellular characteristics. Previously we reported that beta (1,3)glucan is a major component of the Pneumocystis carinii cyst wall. This study shows that administration of aculeacin A, an inhibitor of beta (1,3)glucan biosynthesis, affects cyst wall formation, inhibits cyst maturation, and prevents severe pneumonia in steroid-treated rats. Thus this study not only demonstrates that beta (1,3)glucan is indispensable for growth of the parasite in rats, but suggests a new therapeutic strategy for human pneumocystosis."
|
| 1820056 |
In vitro biosynthesis of Thr2, Leu5, D-Hiv8, Leu10cyclosporin, a cyclosporin-related immunosuppressive peptolide |
None |
Biomed Biochim Acta |
In vitro biosynthesis of Thr2, Leu5, D-Hiv8, Leu10cyclosporin, a cyclosporin-related immunosuppressive peptolide
Abstract
- We were able to prepare an enzyme fraction from crude extracts of the mycelium of the fungus Cylindrotrichum Bonorden, which is capable of synthesizing the new peptolide SDZ 214-103 under consumption of the constitutive amino acids, D-2-hydroxyisovaleric acid, ATP and S-adenosyl-L-methionine. The enzyme does not synthesize CyA, while cyclosporin synthetase does not synthesize the peptolide. Peptolide synthetase has a high molecular weight in the same range as cyclosporin synthetase (about 1.5 MDa).
|
| 1826288 |
Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments |
10.7164/antibiotics.44.172. |
J Antibiot (Tokyo) |
Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments
Abstract
- Anantin, a naturally occurring peptide from Streptomyces coerulescens, binds competitively to the receptor of atrial natriuretic factor (ANF) from bovine adrenal cortex (Kd = 0.6 microM) and acts as ANF antagonist. Protein chemical data and FAB-MS have identified anantin to be a cyclic polypeptide consisting of 17 common L-amino acids. The molecule is highly stable and precludes the application of standard sequencing methods. The primary sequence of anantin was determined by 2D 1H NMR spectroscopy and the application of advanced protein chemical methods to be Gly1-Phe2-Ile3-Gly4-Trp5-Gly6-Asn7-Asp8 -Ile9-Phe10-Gly11-His12-Tyr13-Ser14+ ++- Gly15-Asp16-Phe17. The molecule is cyclized between the beta-carboxyl group of Asp8 and the amino group of Gly1.
|
| 1828464 |
Isolation and characterization of Schizosaccharomyces pombe mutants defective in cell wall (1-3)beta-D-glucan |
10.1128/jb.173.11.3456-3462.1991. |
J Bacteriol |
Isolation and characterization of Schizosaccharomyces pombe mutants defective in cell wall (1-3)beta-D-glucan
Abstract
- Schizosaccharomyces pombe thermosensitive mutants requiring the presence of an osmotic stabilizer to survive and grow at a nonpermissive temperature were isolated. The mutants were genetically and biochemically characterized. In all of them, the phenotype segregated in Mendelian fashion as a single gene which coded for a recessive character. Fourteen loci were defined by complementation analysis. Studies of cell wall composition showed a reduction in the amount of cell wall beta-glucan in three strains (JCR1, JCR5, and JCR10) when growing at 37 degrees C. Galactomannan was diminished in two others. Strains JCR1 and JCR5, with mutant alleles cwg1-1 and cwg2-1, respectively, were further studied. The cwg1 locus was mapped on the right arm of chromosome III, 18.06 centimorgans (cM) to the left of the ade5 marker; cwg2 was located on the left arm of chromosome I, 34.6 cM away from the aro5 marker. (1-3)beta-D-Glucan synthase activities from cwg1-1 and cwg2-1 mutant strains grown at 37 degrees C were diminished, as measured in vitro, compared with the wild-type strain; however, Km values and activation by GTP were similar to the wild-type values. Mutant synthases behaved like the wild-type enzyme in terms of thermostability. Analyses of round shape, lytic behavior, and low (1-3)beta-D-glucan synthase activity in cultures derived from ascospores of the same tetrad showed cosegregation of all these characters. Detergent dissociation of (1-3)beta-D-glucan synthase into soluble and particulate fractions and subsequent reconstitution demonstrated that the cwg1-1 mutant was affected in the particulate fraction of the enzymatic activity while cwg2-1 was affected in the soluble component. The antifungal agents Papulacandin B and Aculeacin A had similar effects on the enzymatic activities of the wild type and the cwg2-1 mutant strain, whereas the cwg1-1 mutant, when growing at 37 degrees C, had a more inhibitor-resistant (1,3)beta-D-glucan synthase. It is concluded that the cwg1+ and cwg2+ genes are related to (1,3)beta-D-glucan biosynthesis.
|
| 1834063 |
Synergistic and antagonistic effects of combinations of cyclosporine A and its metabolites on inhibition of phytohemagglutinin-induced lymphocyte transformation in vitro |
10.1016/0006-2952(91)90452-b. |
Biochem Pharmacol |
Synergistic and antagonistic effects of combinations of cyclosporine A and its metabolites on inhibition of phytohemagglutinin-induced lymphocyte transformation in vitro
Abstract
- Cyclosporine A (CsA) and purified CsA metabolites were tested alone and in combination in cell culture to determine their effects on phytohemagglutinin (PHA)-induced lymphocyte proliferation. CsA was significantly more inhibitory than its metabolites at all concentrations tested (0-1000 ng/mL). CsA exerted maximum inhibition (70% decrease in methyl-3Hthymidine incorporation) at concentrations of 300 ng/mL or greater; metabolites M1, M17, and M21 depressed the response 46, 39, and 23%, respectively, at 300 ng/mL. Metabolites M8, M18, M26, M25, M13, and M203-218 were non-inhibitory. When combinations of M17 and CsA were tested for the effects on PHA-induced lymphocyte transformation, a synergistic effect occurred at combinations of low concentrations of M17 and CsA and an antagonistic effect at the higher concentrations. Of the 49 combinations of CsA and M17 tested, 30 were antagonistic, 16 synergistic and 3 undecided (approaching addition). When 49 combinations of CsA and the non-immunosuppressive metabolite M8 were tested, 29 of the 49 combinations were synergistic, 17 antagonistic, 1 additive and 2 undecided (approaching addition). Of the 29 synergistic combinations, 14 were strongly synergistic. The importance of the interaction of CsA and metabolites to the immunopharmacology of CsA therapy is discussed.
|
| 1841688 |
Multi-conformational peptide dynamics derived from NMR data: a new search algorithm and its application to antamanide |
10.1007/BF01874565. |
J Biomol NMR |
Multi-conformational peptide dynamics derived from NMR data: a new search algorithm and its application to antamanide
Abstract
- A search algorithm, called MEDUSA, is presented which allows the determination of multiple conformations of biomolecules in solution with exchange rate constants typically between 10(3) and 10(7) s-1 on the basis of experimental high-resolution NMR data. Multiples of structures are generated which are consistent as ensembles with NMR cross-relaxation rates (NOESY, ROESY), scalar J-coupling constants, and T1 rho measurements. The algorithm is applied to the cyclic decapeptide antamanide dissolved in chloroform. The characteristic radio-frequency field dependence of the T1 rho relaxation rates found for the NH protons of Val1 and Phe6 can be explained by a dynamical exchange between two structures.
|
| 1846292 |
Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation. |
10.1021/bi00215a008 |
Biochemistry |
Interaction of the alpha beta dimers of the insulin-like growth factor I receptor is required for receptor autophosphorylation.
Abstract
- We have recently found that association of the two alpha beta dimers of the insulin-like growth factor I (IGF I) receptor is required for formation of a high-affinity binding site for IGF I [Tollefsen, S. E., & Thompson, K. (1988) J. Biol. Chem. 263, 16267-16273]. To determine the structural requirements for IGF I activated kinase activity, we have examined the effect of dissociation of the two alpha beta dimers of the IGF I receptor on beta subunit autophosphorylation. The alpha beta dimers formed after treatment with 2 mM dithiothreitol (DTT) at pH 8.75 for 5 min were separated from IGF I receptor remaining as tetramers after DTT treatment by fast protein liquid chromatography on a Superose 6 gel filtration column. Purification of the alpha beta dimers was confirmed by Western blot analysis using 125I-labeled alpha IR-3, a monoclonal antibody to the IGF I receptor. Autophosphorylation of the IGF I receptor (alpha beta)2 tetramer, treated without DTT or remaining after DTT treatment, is stimulated 1.6-2.9-fold by IGF I. In contrast, autophosphorylation of the alpha beta dimers incubated in the presence or absence of IGF I (100 ng/mL) does not occur. Both IGF I receptor dimers and tetramers exhibit similar kinase activities using the synthetic substrate Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly, indicating that the failure to detect autophosphorylation of the IGF I receptor dimers does not result from inactivation of the kinase by DTT treatment. We conclude that autophosphorylation of the IGF I receptor depends upon the interaction of the two alpha beta dimers.
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