Aufgetrennte Tage (German Edition)

Peptide antibiotics and structurally similar agents such as enzyme inhibitors or receptor antagonists, are characterized by interesting biological effects eg various antimicrobial activities, kanzerostatische, cardiotonic, immunomodulatory effects, growth promotion of domestic animals, effects as insecticides, etc. Antibiot 44, , ;..

Antihiot 44, , W. Die Peptaibole bilden eine besondere Untergruppe der Peptidwirkstoffe. The peptaibols form a special subgroup of peptide drugs. Antihiot 27, , ;.. For individual representatives of peptaibols antimicrobial properties and morphogenic effects on fungi have been reported Argoudelis, A.

Antihiot 27, , ; Von Interesse ist insbesondere der biologische Wirkmechanismus der Peptaibole, der eine Ionenkanalbildung in biologischen Membranen beinhaltet siehe zB Grigoriev, P. Acta , 1—5, Of interest, the biological mechanism of action peptaibols that includes an ion channel formation in biological membranes is particularly see, eg, Grigoriev, P. Moreover, it was shown for a number of peptide drugs that interact with receptors of cells or enzymes of cellular signaling pathways and thus cause antagonistic, agonistic, inhibitory and stimulatory effects Miyata, S.

Antibiot 45, , ;..

Download This eBook

Weber et al, J. Antibiot 44, , The measures provided for neuroleptic applications and used agents such as synthetics chlorpromazine, haloperidol , the above-mentioned Ampullosporin have deficiencies, characterized in that unsatisfactory effects are present and that a too high toxicity, unwanted side effects, or poor pharmacokinetics occur. The object of the invention is therefore to provide new compounds of the type of peptaibols with neuroleptic effects available that have potentially improved effects and application properties.

The object is inventively achieved in that the fungus strain Trichoderma sp. DSM is fermented in a nutrient medium containing carbon and nitrogen source and the customary inorganic salts , in which the new neuroleptic effective peptaibols, are preferably accumulated in the culture broth, subsequently isolated from the culture broth, can be obtained in pure form and, if appropriate, converted into chemical derivatives ,. Insbesondere betrifft die Erfindung die folgenden Peptaibole: In particular, the invention relates to the following peptaibols: The invention further relates to a method for producing the peptaibols of the formula I, in particular the peptaibols 1, 2, 3, 4 and 5, which is characterized in that Trichoderma sp.

DSM in a nutrient medium until the compounds are accumulated in the culture broth and allowed to subsequently isolated therefrom.

Ein weiterer Gegenstand der Erfindung betrifft die Verwendung der Peptaibole der Formel I als pharmakologisch wirksame Stoffe, insbesondere als neuroleptische, antipsychotische und anderweitig neurologisch wirksame Arzneimittel. Another object of the invention relates to the use of peptaibols of formula I as pharmacologically active substances, especially as a neuroleptic, anti-psychotic, and otherwise neurologically effective drugs.

Further, the invention provides pharmaceutical compositions that contain one or more peptaibols of formula I, and which are prepared using conventional carriers and excipients relates. The peptaibols invention are represented by the tribe Trichoderma sp. In a medium containing a carbon source, a nitrogen source and the usual mineral salts Trichoderma sp produced. Anstelle des Stammes Trichoderma sp.

DSM peptaibols according to the invention 1, 2, 3, 4 and 5. Instead of the strain Trichoderma sp.

DSM and its mutants and variants can be used. As mutants and variants all those microorganisms of the species that are able to synthesize compounds of the invention apply. Such mutants can be produced in a known manner by physical means, for example irradiation with ultraviolet rays or X-rays or chemical mutagens. Screening for mutants and variants which synthesize compounds of the invention can be carried out in a known test bacteria on the basis of known in the art methods by determining the biological activity of the accumulated in the culture broth agents, for example, by testing the antibiotic activity.

Suitable preferred carbon sources for the aerobic fermentation are assimilable carbohydrates and sugar alcohols such as glucose, lactose, glycerol, mannitol or mixtures thereof, and carbohydrate-containing natural products such as malt extract useful. As the nitrogen source, amino acids, peptides and proteins and their degradation products, such as tryptone, or peptone, also meat extracts, ground seeds, for example of corn, wheat, beans, soybean or the cotton plant, distillation residues from alcohol production, fish meals or yeast extracts are suitable, but also ammonium salts and nitrates ,.

The formation of the peptaibols corresponding to the general structural formula I are good in nutrient media 0. The cultivation is carried out aerobically, for example, submerged with shaking or stirring in shake flasks or using standing cultures in glass bottles. Die Fermentation kann beispielsweise in Steilbrustflaschen, Erlenmeyer- oder Rundkolben verschiedener Volumina erfolgen.

The fermentation can for example take place in reagent bottles, Erlenmeyer or round bottomed flasks of various volumes. Der pH-Wert liegt zwischen 4 und 7, bevorzugt zwischen 4,5 und 6,5. The pH is between 4 and 7, preferably between 4.

Der Mikroorganismus wird unter diesen Bedingungen 5—28 Tage, bevorzugt 7—18 Tage, kultiviert. The microorganism is under these conditions days, preferably days, cultivated.

The fermentation may be carried out on a laboratory scale culture volumes from ml to ml , but also on the production scale volumes up to several m 3. Advantageously, cultivated in several stages, ie one or more precultures initially in a liquid nutrient medium are produced, which then in the actual production medium, the main culture, for example in the ratio 1: The peptaibols invention are included in varying proportions in the culture broth, preferably in the mycelium.

The isolation of the peptaibols from the culture broth by known methods, taking into account the chemical, physical and biological properties of the products. To isolate the peptaibols water-insoluble organic solvent such as ethyl acetate is added to the culture solution and the culture broth extracted completely at the end of fermentation emergent laboratory scale. For the isolation of the new peptaibols from submerged culture fermentation batches of the culture medium and the mycelium is separated at the end and the mycelium with organic solvents, such as methanol or acetone, preferably methanol extracted.

Further quantities of Peptaibolen obtained by extraction of the separated mycelium from the culture solution with water-insoluble organic solvents such as ethyl acetate. After concentrating the extracts and optionally re-extraction of the methanol extract of the mycelia with water-insoluble organic solvents such as ethyl acetate or dichloromethane, The isolation of the peptaibols using conventional chromatographic adsorbents or carrier materials such as silica or organophilic dextran gels.

The antibacterial effects of peptaibols can be identified by the specialist admitted methods such as the determination of minimum Hemmzonenkonzentration MIC in the agar plate European Pharmacopoeia 3 rd Edition, Official Austrian edition, published by Austria, pp The new peptaibols are effective against bacteria, preferably against Gram-positive organisms such as Bacillus subtilis ATCC rd. The peptaibols invention are effective strong neuroleptic in experimental animals mouse.

• Beowulf: The Storybook Version!
• From GED to PhD: The Autobiography of Dr. Bon Blossman;
• Translate Tag from German to English.
• Designing User Friendly Augmented Work Environments: From Meeting Rooms to Digital Collaborative Spaces (Computer Supported Cooperative Work).
• An Elementary Treatise on Electricity: Second Edition (Dover Books on Physics).

Lower long-lasting body temperature as well as of how the well-known neuro-therapeutic chlorpromazine. The University of Chicago Press, Felix Meiner Verlag, [] Urteil und Erfahrung: Fichtes System der Sittenlehre: Unity and diversity in European culture c.

1. Passion!
2. Meaning of "Filterpapier" in the German dictionary.
3. New Books (Germanic Studies), August - University Libraries Washington University in St. Louis.

Oxford ; New York: De Gruyter Oldenbourg, []. Houndmills, Basingstoke, Hampshire ; New York: Hildegard of Bingen and musical reception: Cambridge University Press, Pendragon Press, [] Ernst Barlach: Plastik, Zeichnungen, Druckgraphik, Galerie Georg Nothelfer, [] Fragments of metropolis Berlin: University of Toronto Press, [] Planetary modernisms: Columbia University Press, [] Fictions of the war on terror: Edinburgh University Press, [] Digital scholarly editing: Farnham, Surrey ; Burlington, VT: Ashgate, [] Born translated: European cinema and television: Oxford University Press, University of Pennsylvania Press, c Louis History Story illustration W.

Gass WU Biology Dept.