| 1446006 |
Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66 |
10.1021/tx00029a011. |
Chem Res Toxicol |
Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66
Abstract
- A hepatotoxic strain of cyanobacterium Anabaena sp. 66 was isolated from a hepatotoxic water bloom sample in Lake Kiikkara, Finland. Four cyclic heptapeptide hepatotoxins were isolated and purified by HPLC from cultured cells of this organism. The structures of three new homotyrosine (Hty) containing toxins, Dha7microcystin-HtyR (Dha = dehydroalanine) (1), D-Asp3,Dha7microcystin-HtyR (2), and L-Ser7microcystin-HtyR (3), were assigned, based upon amino acid analyses using both a Waters Pico Tag HPLC system and chiral capillary GC, 1H NMR, fast atom bombardment mass spectrometry (FABMS), and collisionally induced tandem FABMS. A new homophenylalanine (Hph) variant of 1, Dha7microcystin-HphR (4), was also obtained as a minor component. Compound 3 is most likely a biosynthetic precursor of 1. The four new toxins did not have an N-methyl group at the dehydroamino acid or its precursor unit.
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| 1448848 |
High-performance liquid chromatographic analysis of cyclosporin G (Nva2-cyclosporine) in human blood |
10.1097/00007691-199210000-00010. |
Ther Drug Monit |
High-performance liquid chromatographic analysis of cyclosporin G (Nva2-cyclosporine) in human blood
Abstract
- A sensitive high-performance liquid chromatographic method for the analysis of the immunosuppressant cyclosporin G (OG 37-325, Nva2-cyclosporine, CsG) in whole blood has been developed. Sample preparation, employing cyclosporin A (CsA) as internal standard, involves organic extraction with methyl t-butyl ether under sequential acidic and basic conditions. Chromatography is performed using a 2 mm inside diameter x 25 cm column packed with 5 microns octyl (C8) material. An isocratic mobile phase comprised of acetonitrile:methanol:water, at a flow rate of 0.4 ml/min, is utilized. Separation is monitored at 230 nm. Data are also presented that demonstrate the use of CsG as an alternative internal standard to cyclosporin D for liquid chromatographic determinations of CsA.
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| 1449472 |
Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa |
10.1016/0006-291x(92)91542-x. |
Biochem Biophys Res Commun |
Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa
Abstract
- Two unique antimicrobial peptides named brevinin-1 and -2 were isolated from the skin of the frog, Rana brevipoda porsa. Both of the peptides did not have any structural homology with bombinin nor magainin; the frog skin derived-antimicrobial peptides isolated from Bombina and Xenopus, nor even with other known antimicrobial peptides of non-amphibian origin. The minimum inhibitory concentration of brevinin-1 against the growth of St. aureus and E. coli was determined to be 8 micrograms/ml and 34 micrograms/ml while that of brevinin-2 was 8 micrograms/ml and 4 micrograms/ml, respectively, indicating the difference of the two peptides in the antimicrobial selectively on Gram-positive and Gram-negative bacteria.
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| 1467551 |
Thermospray high-performance liquid chromatography/mass spectrometric determination of cyclosporins |
10.1002/rcm.1290061111. |
Rapid Commun Mass Spectrom |
Thermospray high-performance liquid chromatography/mass spectrometric determination of cyclosporins
Abstract
- The cyclic undecapeptides cyclosporin (Csp) A, CspD and dihydro CspC (HCspC) were analyzed by high-performance liquid chromatography/thermospray-mass spectrometry (HPLC/TSP-MS) on line with a UV detector. Positive ion partial (1000-1300 u) mass spectra of these compounds could be obtained with 1-2 pmol injected on column. Mass spectra were characterized by signals corresponding to the M+H ions as well as fragment ions derived from the loss of 112 (CspA and CspD) or 44, 114 and 114 + 44 (HCspC) mass units from the parent ion. The same qualitative profile was observed for negative-ion acquisition where the ions were formed by proton abstraction. The application of the technique to the characterization of CspA and its major hydroxylated and dealkylated metabolites in human blood samples is presented.
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| 1470163 |
[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes] |
None |
Nihon Geka Gakkai Zasshi |
[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes]
Abstract
- A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.
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| 1472036 |
Identification of a disulfide bridge connecting the alpha-subunits of the extracellular domain of the insulin receptor. |
10.1016/0006-291x(92)92250-2 |
Biochem. Biophys. Res. Commun. |
Identification of a disulfide bridge connecting the alpha-subunits of the extracellular domain of the insulin receptor.
Abstract
- The alpha 2 beta 2 structure of the insulin receptor has previously been shown to involve one disulfide bridge between the alpha-subunits in the region containing Cys435, Cys468 and Cys524. We have digested the soluble extracellular domain of the insulin receptor with succinylated trypsin, partially separated the resulting peptides, and sequenced a number of fractions. The peptides containing Cys435 and Cys468 appeared in the same fraction, indicating that these two form a disulfide bond, and in another fraction we found the sequence of the peptide containing Cys524. Since it has been shown that the extracellular domain of the insulin receptor has no free thiols and since no other sequences containing cysteine were found in these fractions, we conclude that Cys524 forms a disulfide bond to the Cys524 in the other alpha-subunit.
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| 1472056 |
A novel anti-HIV synthetic peptide, T-22 (Tyr5,12,Lys7-polyphemusin II) |
10.1016/0006-291x(92)92280-b. |
Biochem Biophys Res Commun |
A novel anti-HIV synthetic peptide, T-22 (Tyr5,12,Lys7-polyphemusin II)
Abstract
- Tachyplesin and polyphemusin are antimicrobial peptides recently isolated from the hemocytes of horseshoe crabs (Tachypleus tridentatus and Limulus polyphemus). We synthesized them and their analogs and examined their antiviral activity against human immunodeficiency virus (HIV) type 1 in vitro. The infection of human T cells with the virus was markedly inhibited by some of them at low concentrations. In this structure-activity study, we found that Tyr5,12, Lys7-polyphemusin II, which was designated as T22, had extremely high anti-HIV activity. Its 50% inhibitory concentration (EC50) was 0.008 micrograms/ml, while its 50% cytotoxic concentration (CC50) was 54 micrograms/ml and these values were comparable to those of AZT. This result indicates that T22 would be a potential candidate for the therapy of HIV infection.
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| 1472654 |
Solution conformations of two flexible cyclic pentapeptides: cyclo(Gly-Pro-D-Phe-Gly-Ala) and cyclo(Gly-Pro-D-Phe-Gly-Val) |
10.1002/bip.360321213. |
Biopolymers |
Solution conformations of two flexible cyclic pentapeptides: cyclo(Gly-Pro-D-Phe-Gly-Ala) and cyclo(Gly-Pro-D-Phe-Gly-Val)
Abstract
- In an effort to explore the residue preferences in three-residue reverse turns (so-called gamma-turns), two cyclic pentapeptides--cyclo(Gly1-Pro2-D-Phe3-Gly4-Ala5) (I) and cyclo(Gly1-Pro2-D-Phe3-Gly4-Val5) (II)--have been synthesized and analyzed by nmr. It was anticipated that the Gly-Pro-D-Phe-Gly portions of these molecules would favor a beta-turn conformation, leaving the remainder of the molecule to adopt a gamma turn, as seen in several previously studied model cyclic pentapeptides. The nmr data for both peptides in CDCl3 (5% DMSO-d6) and in neat DMSO-d6 indicate that the most populated conformation contains a distorted beta turn around Pro2-D-Phe3, which includes a gamma turn around D-Phe3. The distortion in the beta turn does not impede the formation of an inverse gamma turn around residue 5, and indeed, this conformation is observed in both peptides. Both the alanine and the bulkier valine residues are therefore found to be compatible with an inverse gamma turn. Molecular dynamics simulations on the title peptides are reported in the following paper. These simulations indicate that there is conformational flexibility around the D-Phe3-Gly4 peptide bond, which enables the formation of the gamma turn around D-Phe3. The third paper in this series explores the impact of a micellar environment on conformational equilibria in II.
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| 1476708 |
Virotoxins polymerize actin and induce membrane fragmentation in cytoplasmic preparations of Amoeba proteus |
10.1139/o92-110. |
Biochem Cell Biol |
Virotoxins polymerize actin and induce membrane fragmentation in cytoplasmic preparations of Amoeba proteus
Abstract
- Virotoxins and phalloidin are peptides that induce actin polymerization in vitro. We have compared the effect of five virotoxins and phalloidin on the ultrastructure of spread preparations of Amoeba proteus cytoplasm. Like phalloidin, the five virotoxins induce polymerization of cytoplasmic actin. Moreover, the virotoxins, but not phalloidin, induce membrane fragmentation in small spherical vesicles. We, therefore, conclude that these virotoxins may have another membrane-bound target besides actin.
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| 1477912 |
Structures and conformations of metabolites of antitumor cyclic hexapeptides, RA-VII and RA-X |
10.1248/cpb.40.2984. |
Chem Pharm Bull (Tokyo) |
Structures and conformations of metabolites of antitumor cyclic hexapeptides, RA-VII and RA-X
Abstract
- Metabolites of antitumor cyclic hexapeptides, RA-VII and -X which were isolated from Rubia cordifolia were studied by hepatic microsomal biotransformation in rats and in bile juice of rabbits to which these drugs were administered intravascularly. Their structures and conformations were elucidated by two-dimensional nuclear magnetic resonance techniques, temperature effect on NH protons and nuclear Overhauser effect experiments. Specific N-demethylation of Tyr-3, O-demethylation and hydroxylation at aromatic rings of Tyr-3 and -5 were observed. Compared with metabolites of RA-VII, most of RA-X was excreted unchanged in the bile juice. Relationship among their structures, conformations and antitumor activities is also discussed.
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| 1485340 |
Two new L-serine variants of microcystins-LR and -RR from Anabaena sp. strains 202 A1 and 202 A2 |
10.1016/0041-0101(92)90521-6. |
Toxicon |
Two new L-serine variants of microcystins-LR and -RR from Anabaena sp. strains 202 A1 and 202 A2
Abstract
- Two new microcystins, L-Ser7microcystin-LR (1) and L-Ser7microcystin-RR (2), were isolated from a filamentous fresh water cyanobacterium (blue-green alga), Anabaena sp. strain 202 A1, along with the two major toxins, Dha7microcystin-LR (3) and Dha7microcystin-RR (4) and their minor components the D-Asp variants D-Asp3,Dha7microcystin-LR (5) and D-Asp3,Dha7microcystin-RR (6). Anabaena sp. strain 202 A1 also produced another new toxin, whose structure is tentatively proposed as D-Asp3,L-Ser7microcystin-XR (7), where X is a leucine homologue. Anabaena sp. strain 202 A2 produced one new microcystin, 1, and three known microcystins, 3, 4, and 5. The structures of the toxins were assigned based on their amino acid analyses, and fast atom bombardment mass spectrometry data.
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| 1485341 |
Two methyl ester derivatives of microcystins, cyclic heptapeptide hepatotoxins, isolated from Anabaena flos-aquae strain CYA 83/1 |
10.1016/0041-0101(92)90522-7. |
Toxicon |
Two methyl ester derivatives of microcystins, cyclic heptapeptide hepatotoxins, isolated from Anabaena flos-aquae strain CYA 83/1
Abstract
- Cultured cells of Anabaena flos-aquae strain CYA 83/1, isolated from Lake Edlandsvatn, Norway, produced two microcystin mono-methyl ester derivatives (1 and 2) at the D-Glu unit in addition to microcystin-LR (3), D-Asp3microcystin-LR (4), microcystin-RR (5), and D-Asp3microcystin-RR (6). Structures of these compounds were assigned based on their amino acid analysis with a Waters Pico Tag HPLC system plus fast atom bombardment mass spectrometry (FABMS), including tandem FABMS, analysis on the two new microcystins, D-Glu(OCH3)6microcystin-LR (1) and D-Asp3, D-Glu(OCH3)6microcystin-LR (2). Toxicity data were not obtained for 1 and 2 because of the small amounts isolated from the cells.
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| 1485342 |
Isolation and structures of microcystins from a cyanobacterial water bloom (Finland) |
10.1016/0041-0101(92)90523-8. |
Toxicon |
Isolation and structures of microcystins from a cyanobacterial water bloom (Finland)
Abstract
- A hepatotoxic cyanobacterial (blue-green algal) water bloom was collected from a constructed water reservoir in Finland. The water bloom contained two cyanobacterial species, Microcystis aeruginosa and Aphanizomenon flos-aquae. Two hepatotoxins, 1 and 2, were isolated from extracts of lyophilized cells. The structures of 1 and 2 were assigned based upon their amino acid analyses on a Waters Pico Tag HPLC system and a chiral GC capillary column (Chirasil Val III), fast atom bombardment mass spectrometry (FABMS), high resolution FABMS, and tandem FABMS data. Toxin 1 was identical to a previously reported compound, D-Asp3microcystin-RR. Toxin 2 was new and was assigned the structure D-Asp3microcystin-YR.
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| 1485343 |
Isolation and structures of five microcystins from a Russian Microcystis aeruginosa strain CALU 972 |
10.1016/0041-0101(92)90524-9. |
Toxicon |
Isolation and structures of five microcystins from a Russian Microcystis aeruginosa strain CALU 972
Abstract
- Five microcystins were obtained from Microcystis aeruginosa strain CALU 972 isolated from a hepatotoxic water bloom collected in Lake Kroshnosero (Russia). The structure of a new toxin (1) was determined as Dha7microcystin-YR by amino acid analyses and fast atom bombardment mass spectrometry, and the toxins 2, 3, 4, and 5 were assigned the structures as Dha7microcystin-LR, D-Asp3,Dha7microcystin-LR, Dha7microcystin-RR, and D-Asp3,Dha7microcystin-RR, respectively, by direct comparison with authentic samples.
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| 1490876 |
Pneumocandins from Zalerion arboricola. I. Discovery and isolation |
10.7164/antibiotics.45.1853. |
J Antibiot (Tokyo) |
Pneumocandins from Zalerion arboricola. I. Discovery and isolation
Abstract
- HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.
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