| 7997262 |
Crystal structure of the tyrosine kinase domain of the human insulin receptor |
10.1038/372746a0. |
Nature |
Crystal structure of the tyrosine kinase domain of the human insulin receptor
Abstract
- The X-ray crystal structure of the tyrosine kinase domain of the human insulin receptor has been determined by multiwavelength anomalous diffraction phasing and refined to 2.1 A resolution. The structure reveals the determinants of substrate preference for tyrosine rather than serine or threonine and a novel autoinhibition mechanism whereby one of the tyrosines that is autophosphorylated in response to insulin, Tyr 1,162, is bound in the active site.
|
| 7999137 |
Antimicrobial peptides from the skin of a Korean frog, Rana rugosa |
10.1006/bbrc.1994.2757. |
Biochem Biophys Res Commun |
Antimicrobial peptides from the skin of a Korean frog, Rana rugosa
Abstract
- Six antimicrobial peptides, named gaegurins, were isolated from the skin of a Korean frog, Rana rugosa, and their amino acid sequences were determined by automated Edman degradation. All peptides contain two invariant cysteine residues, one at their C-terminus and the second at the seventh position from the C-terminus. The heptapeptides containing these two cysteine residues, which we designate 'Rana boxes', are conserved in the antimicrobial peptides derived from other Rana species. Each peptide manifested a broad spectrum of antimicrobial activity against Gram positive and Gram negative bacteria, fungi and protozoa with slightly different specific activities. All gaegurins manifest very little or no hemolytic activity. These properties provide the potential for application of these peptides to effective therapeutic agents for control of pathogenic microorganisms."
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| 8002397 |
Synthesis of PF1022A, an anthelmintic cyclodepsipeptide |
10.7164/antibiotics.47.1322. |
J Antibiot (Tokyo) |
Synthesis of PF1022A, an anthelmintic cyclodepsipeptide
Abstract
|
| 8010869 |
Immunosuppressive activity of some peptides related to cycloamanide A (CyA A) and to the active fragment of a peptide immunomodulator from ovine colostrum |
None |
Arch Immunol Ther Exp (Warsz) |
Immunosuppressive activity of some peptides related to cycloamanide A (CyA A) and to the active fragment of a peptide immunomodulator from ovine colostrum
Abstract
- A series of linear and cyclic hexapeptides, consisting of: Phe-Phe-Val-Pro-Gly-Ala, Tyr-Phe-Val-Pro-Gly-Ala, Phe-Tyr-Val-Pro-Gly-Ala, D-Phe-Tyr-Val-Pro-Gly-Ala, D-Tyr-Phe-Val-Pro-Gly-Ala, D-Tyr-Tyr-Val-Pro-Gly-Ala, c-(Phe-Tyr-Val-Pro-Gly-Ala-), c-(Tyr-Tyr-Val-Pro-Gly-Ala-) was synthesized and examined for the influence on humoral immune response by the plaque forming cell test. The peptides are related to Tyr-Val-Pro-Gly-Phe-Pro hexapeptide (an active fragment of immunomodulatory polypeptide found in sheep colostrum) and to the retro-sequence of cycloamanide A, a peptide immunosuppressor present in the mushroom Amanita phalloides. We found that substitution of one or both phenylalanine residues of the linear retro-sequence of cycloamanide A by tyrosine, enhances the immunosuppressive activity of the peptide. The inversion of configuration of N-terminal aromatic residues preserves the immunosuppressive activity. However, in this case, application of higher doses of the peptides decreases their activity. The highest immunosuppressive potency was found for Phe-Tyr-Val-Pro-Gly-Ala hexapeptide, which is most closely related to the active fragment of a peptide immunomodulator from the ovine colostrum, investigated by us previously.
|
| 8013647 |
Identification of a new member of the protegrin family by cDNA cloning |
10.1016/0014-5793(94)00493-5. |
FEBS Lett |
Identification of a new member of the protegrin family by cDNA cloning
Abstract
- The porcine leukocyte protegrins are a family of cysteine-rich antimicrobial peptides the primary structures of which combine features of defensins and tachyplesins. We cloned three protegrins from porcine bone marrow mRNA by PCR, including one (PG-4) that was previously unknown. The 691 bp protegrin cDNAs were > 98.8% identical, and each was surrounded by highly conserved 5' and (in some instances) 3' sequences present in structurally dissimilar antimicrobial and LPS-binding peptides of animal leukocytes."
|
| 8018309 |
Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella |
10.1107/s010827019300811x. |
Acta Crystallogr C |
Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella
Abstract
- The structure of crystals of patellamide A (13-methyl-9,23-bis(1-methylethyl)-2,16-bis(1-methylpropyl)-14,-28-di oxa-7,21- dithia-3,10,17,24,29,30,31,32- octaaza-pentacyclo24.2.1.1(5,8).1(12,15).1(19,22dotriac onta-1(29),5,- 8(30),15(31),19,22(32)-hexaene-4,11,18,25-tetraone methanol solvate monohydrate, C35H49N8O6S2.-CH4O.H2O), a cytotoxic cyclic peptide having a non-C2-symmetric methyl group, shows the C2-symmetric and saddle-shaped rectangular conformation where the methyl group is disordered into two C2-symmetric positions. The water and methanol solvents were located on the crystallographic diad axis and were held by hydrogen bonds and van der Waals contacts with the polar ring N atoms and non-polar D-Val side-chain atoms, respectively.
|
| 8027972 |
Derivatives of a novel cyclopeptolide. 1. Synthesis, antifungal activity, and structure-activity relationships |
10.1021/jm00039a002. |
J Med Chem |
Derivatives of a novel cyclopeptolide. 1. Synthesis, antifungal activity, and structure-activity relationships
Abstract
- The synthesis of a series of derivatives of the novel antifungal cyclopeptolide 1, which consists of nine S-amino acids and R-lactic acid, is described. Besides functional group variation of MeAsp4 (esters 2a-d, amides 3a-d, alcohol 4, and its derivatives) and Tyr(Me)9 (demethyl derivative 8, ethers 12a-f, 13, and oxidative degradation of the phenyl group to 14), opening of the lactone by LiOH in THF/H2O allowed manipulation of the hydroxy group of R-Hypr10 in the resulting acyclic peptide 15. Recyclization of 15 under Mitsunobu conditions followed by deprotection led to the S-Hypr10 analogue 17 of 1. Cyclic decapeptides 33 and 34 as well as cyclic undecapeptides 35 and 36 were obtained via the corresponding modified linear peptides 23, 24, 27, and 28 by cyclization. Methylation of all secondary amide groups by CH3I and KH/18crown6 gave the permethylated compound 37. Two of the derivatives (17 and 34) showed superior activities against yeasts in vitro at pH 6.5 as compared to 1, but not at a lower pH (4.5).
|
| 8028448 |
Effects of a new endothelin antagonist, TAK-044, on post-ischemic acute renal failure in rats |
10.1016/0024-3205(94)00732-2. |
Life Sci |
Effects of a new endothelin antagonist, TAK-044, on post-ischemic acute renal failure in rats
Abstract
- Protective effects of a new endothelin (ET) receptor antagonist, TAK-044, were studied in a model of acute renal failure (ARF) in rats. ARF was induced by clamping the left renal pedicle for 45 minutes with contralateral nephrectomy and subsequent reperfusion of the left kidney. Plasma creatinine concentration (Pcr) increased to 2.28 mg/dl 24 hours after reperfusion of the ischemic kidney. Intravenous administration of TAK-044 (1-10mg/kg) prior to renal occlusion dose-dependently but partially attenuated the increase in Pcr and the morphological damages of the kidney. ET-1 and ET-3 increased perfusion pressure in isolated kidney preparations with similar potency, indicating that the renal vasoconstriction evoked by these ET isomers is mainly via ETB receptors, and TAK-044 (10nM) shifted the ET-1 dose-response curve to the right by a factor about 10. In a rat renal membrane fraction, ET-1 showed competitive inhibition of specific 125IET-1 binding with an IC50 value of 0.34nM and a Hill slope of 1.10. ET-3 did so with a higher IC50 value (3.3nM) and a lower Hill slope (0.56), suggesting that rat kidney contains both ETA and another receptor subtype, probably ETB. TAK-044 inhibited ET-1 binding with an IC50 value of 6.6nM and a Hill slope of 0.41. Plasma concentrations of immunoreactive TAK-044 were maintained over 7nM for 8 hours following i.v. injection of 10mg/kg TAK-044. These results suggest that endogenous ET is involved in the pathogenesis of post-ischemic ARF, at least, in part and that TAK-044 provided protective effects against ARF by blocking ET receptors, possibly both ETA and ETB receptors in renal vasculature and parenchymal cells.
|
| 8040048 |
Aselacins, novel compounds that inhibit binding of endothelin to its receptor. I. The producing organism, fermentation and biological activity |
10.7164/antibiotics.47.523. |
J Antibiot (Tokyo) |
Aselacins, novel compounds that inhibit binding of endothelin to its receptor. I. The producing organism, fermentation and biological activity
Abstract
- A radioligand test to detect inhibitors of endothelin-1 binding to its receptors in bovine atrial and porcine cerebral membranes was used to screen fungal metabolites from stationary fermentations. Inhibitory activity, observed in culture extracts of two Acremonium species, led to the discovery of aselacins A, B and C. Aselacin A inhibits binding to both membrane fractions with IC50s of approximately 20 micrograms/ml.
|
| 8040049 |
Aselacins, novel compounds that inhibit binding of endothelin to its receptor. II. Isolation and elucidation of structures |
10.7164/antibiotics.47.528. |
J Antibiot (Tokyo) |
Aselacins, novel compounds that inhibit binding of endothelin to its receptor. II. Isolation and elucidation of structures
Abstract
- Three novel compounds, named the aselacins, which inhibit the binding of endothelin to its receptor have been isolated from two related Acremonium species of fungi grown in stationary culture. These compounds are cyclic pentapeptolides with a ring formed by cycloGly-D-Ser-D-Trp-beta-Ala-L-Thr and an additional exocyclic D-Gln to which is attached a functionalized long chain fatty acid. The aselacins differ in the functionalization of this acid. The structures of the aselacins were determined by amino acid analysis, mass spectrometry and evaluation of 1-D and 2-D homonuclear and heteronuclear 1H, 13C and 15N NMR spectra in protic and aprotic solvents. The stereochemistry of the amino acids present was elucidated by chiral HPLC of hydrolyzed compound.
|
| 8050589 |
Molecular structure of the cyanobacterial tumor-promoting microcystins |
10.1016/0014-5793(94)00680-6. |
FEBS Lett |
Molecular structure of the cyanobacterial tumor-promoting microcystins
Abstract
- The three-dimensional structure of the two hepatotoxic microcystins LR and LY has been determined by two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy and distance geometry calculations. For the microcystin LY a single family of highly convergent structures was obtained. This family is characterized by a relatively compact boat-like ring structure with the large side chain of the Adda residue protruding from the concave side, in close proximity to the Tyr side chain. Conversely, for the microcystin LR the calculations result in three conformational families characterized by an even more compact ring structure. The Adda and Arg side chains protrude from the ring distal from one another caused by the repulsion between the guanido function of Arg and the hydrophobic Adda. The lower toxicity of the LY microcystin could result from the restricted access of the Adda side chain, an essential residue for activity, which results from the close proximity of the aromatic Tyr residue. A significant enthalpic cost would be expected for disturbance of this hydrophobic collapse and correspondingly lower binding affinity to receptor molecules would be predicted. From the structures of the two related microcystins, and homology with other known toxins, we propose a working hypothesis of the Adda side chain interacting with a hydrophobic pore of the phosphatases while the rest of the microcystin acts as a scaffold to help stabilize the interdigitation of the Adda with additional intermolecular interactions.
|
| 8069966 |
Complex formation of cyclo(L-Phe-L-Pro)4 with noradrenaline hydrochloride |
10.1248/cpb.42.1146. |
Chem Pharm Bull (Tokyo) |
Complex formation of cyclo(L-Phe-L-Pro)4 with noradrenaline hydrochloride
Abstract
- The 13C-NMR spectrum of cyclo(L-Phe-L-Pro)4 (1) and DL-noradrenaline hydrochloride (DL-NA.HCl) in a mixture of CDCl3 and CD3OD suggested the formation of a complex, which was demonstrated to be 1:1 from examination of the titration curves. The complex retained the C2-symmetric conformation of 1 containing two cis-peptide bonds, and was linked through hydrogen bonds between the carbonyl groups of the Phe1 and Pro2 residues, and the ammonium moiety of NA.HCl.
|
| 8071120 |
Pneumocandin D0, a new antifungal agent and potent inhibitor of Pneumocystis carinii |
10.7164/antibiotics.47.755. |
J Antibiot (Tokyo) |
Pneumocandin D0, a new antifungal agent and potent inhibitor of Pneumocystis carinii
Abstract
- Pneumocandin D0 (9), a new member of the echinocandin class of antifungal agents, has been isolated as a minor constituent from fermentation broths of the filamentous fungi Zalerion arboricola (ATCC 20957). The structure of 9 has been determined mainly on the basis of spectroscopic analysis and by comparison with published data for similar compounds. To date, pneumocandin D0 has been found to be the most potent inhibitor of Pneumocystis carinii development in vivo within the natural-occurring echinocandin family of antifungal agents.
|
| 8071121 |
Ustiloxins, antimitotic cyclic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens |
10.7164/antibiotics.47.765. |
J Antibiot (Tokyo) |
Ustiloxins, antimitotic cyclic peptides from false smut balls on rice panicles caused by Ustilaginoidea virens
Abstract
- Ustiloxins A (1a), B (1b), C (1c), D (1d) and E (1e), antimitotic peptides, have been isolated from the water extract of false smut balls caused on the panicles of rice plant by a fungus Ustilaginoidea virens. The structure of 1b was assigned from its spectral property and its amino acid analysis in relation to 1a whose structure was determined previously by a combination of X-ray crystallographic and amino acid analyses. Structures of 1c and 1d were elucidated by their spectroscopic data, specially based on their 1H and 13C NMR spectra. Bioactivities of these compounds against microtubule assembly as well as mammal, plant and fungal cells have been studied.
|
| 8071320 |
Crystallographic structure of human gamma-thrombin |
None |
J Biol Chem |
Crystallographic structure of human gamma-thrombin
Abstract
- In an effort to prepare crystals and determine the structure of alpha-thrombin complexed to a synthetic peptide inhibitor (MDL-28050) of the hirudin 54-65 COOH-terminal region, it was discovered that the crystals were not those of the complex but of gamma-thrombin. Gel electrophoresis studies revealed that autolytic degradation had occurred prior to crystallization. NH2-terminal sequence analysis of these autolytic fragments confirmed the gamma-thrombin product (cleavages at Arg75-Tyr76 and/or Arg77A-Asn78, and Lys149E-Gly150; chymotrypsinogen numbering) with a minor amount of another autolysis product, beta-thrombin (first two cleavages only). The final structure has an R-factor of 0.156 for 7.0-2.5-A data, and includes 186 water molecules. A comparison of gamma-thrombin with the thrombin structure in the alpha-thrombin-hirugen complex revealed that the two structures agreed well (r.m.s. delta = 0.39 A for main chain atoms). These structures possess uninhibited active sites where the disposition of the catalytic triad residues is nearly identical. The electron density in the vicinity of the gamma-thrombin cleavage regions is poor, and only becomes well-defined several residues prior to and after the actual cleavage sites. The extensive disorder evoked by beta-cleavage(s) in the Lys70-Glu80 loop region indicates that this part of the molecule is severely disrupted by autolysis and is the reason exosite functions are dramatically impaired in beta-and gamma-thrombin. Since autolysis did not lead to a major reorganization of the folded structure of alpha-thrombin, the likely structural features of the interaction of thrombin substrate with thrombin enzyme during beta-cleavage have been modeled by docking the exosite region of one molecule at the active site of another.
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