Cyclosporin A and C

Dreyfuss, M.; Härri, E.; Hofmann, H.; Kobel, H.; Pache, Walter; Tscherter, H.

doi:10.1007/bf00928431

Cited by 293 publications

(111 citation statements)

References 6 publications

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“…Records of the colonic temperature occured 0. 5,1,3,5,8,24,48,96 hours after administration of peptaibols. Hypothermia potency peak-time of hypothermic response and duration was recorded by use of a single dose response.…”

Section: In Vivo Determination Of Neuroleptic Activitymentioning

confidence: 99%

Ampullosporin, a New Peptaibol-type Antibiotic from Sepedonium ampullosporum HKI-0053 with Neuroleptic Activity in Mice.

et al. 1997

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Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phomadestructive causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.Microbial metabolites inducing the morphogenesis and cytodifferentiation of other microbes have been shown to display interesting pharmacological activities1}. Recently we described a fungal strain, Phomadestructive which responded during surface cultivation to small amounts of cyclosporin A by the formation of a blackish pigment2). In a screening for similar inducers of pigment formation we discovered the chrysospermins2'3) as new peptaibol-type antibiotics4) from Apiocrea chrysosperma which showed the same effect as this immunomodulatory compound. But several other peptaibols such as alamethicin4) and bergofungin5) failed to afford this phenomenon.In order to obtain moreinformation about structureactivity relationships of the peptaibol antibiotics as inducers of pigment formation, we searched for other peptides from fungal cultures that could affect Phoma destructiva. Here, we report on a newpeptaibol-type antibiotic, ampullosporin (I) from Sepedonium ampullosporum HKI-0053, which is active in the same manner as described for cyclosporin A and chrysospermins2). Moreover, ampullosporin was found to induce hypothermia in mice suggesting a neuroleptic activity. Materials and MethodsMicroorganism and Cultivation Sepedonium ampullosporutn HKI-0053 was obtained from the culture collection of the Hans-Knoll-Institute of Natural Product Research Jena (Germany). The strain SEPT. 1997 was deposited in the DSMZculture collection (Braunschweig, Germany) under the registry number DSM 10602. Fifteen days agar-plate cultures (25°C) were prepared as seed mediumcomposed of malt extract 4%, yeast extract 0.4%, agar 1.5% and deionized water, pH 6.0. Four to five cm2 areas of the agar-plate cultures were used to inoculate a liquid mediumcomposed of glycerol 3%, glucose 1%, peptone 0.5%, NaCl 0.2%, molecular sieve (0.5nm, Merck) 0.1% and agar 0.1%, pH 7.0. The surface cultivation was carried out at 25°C in 1 liter Erlenmeyer flasks containing 100ml of the above medium for two weeks. Subsequently, the whole culture broth was extracted twice with two volumes of ethyl acetate.Instruments and Analytical Methods HPLCwas carried out using a Gilson binary gradient HPLCsystem equipped with a UV detector (210nm). Positive ion FABmass spectra were recorded on an AMD402 double-focussing mass-spectrometer with BE geometry (AMD, Intectra, Harpstedt, Germany). Ions were produced by Cs+ ion bombardment generated by a Cs+ gun (liquid SIMSsystem, AMDIntectra). Peptide solutions were mixed with 3-nitrobenzyl alcohol as matrix on the FABprobe tip. High-resolution...

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Section: In Vivo Determination Of Neuroleptic Activitymentioning

confidence: 99%

Ampullosporin, a New Peptaibol-type Antibiotic from Sepedonium ampullosporum HKI-0053 with Neuroleptic Activity in Mice.

et al. 1997

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“…Cyclosporin A (CsA), a secondary metabolite of Tolypocladium inflatum, is a hydrophobic, undecameric, cyclic peptide with both immunosuppressant and cytotoxic activities (1). Proteins with high affinity for CsA, termed cyclophilins, have been purified from a number of eukaryotic sources (2)(3)(4)(5)(6)(7)(8).…”

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confidence: 99%

A yeast cyclophilin gene essential for lactate metabolism at high temperature.

Davis

Becker

Heitman

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…All three immunosuppressants also possess antifungal activities (9,20,55), and CsA and rapamycin were first discovered as antifungal agents. Moreover, fungal homologs of cyclophilin (16,22,53) and FKBP (41,54,56) have been identified.…”

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confidence: 99%