EP0240501A1 - A novel peptide, a microbiological process for its production and use theeof as an antibiotic, cytotoxic and phythotoxic agent - Google Patents
A novel peptide, a microbiological process for its production and use theeof as an antibiotic, cytotoxic and phythotoxic agentInfo
- Publication number
- EP0240501A1 EP0240501A1 EP86901996A EP86901996A EP0240501A1 EP 0240501 A1 EP0240501 A1 EP 0240501A1 EP 86901996 A EP86901996 A EP 86901996A EP 86901996 A EP86901996 A EP 86901996A EP 0240501 A1 EP0240501 A1 EP 0240501A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- iii
- cytotoxic
- phythotoxic
- formula
- leu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/02—Linear peptides containing at least one abnormal peptide link
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
- C12N1/145—Fungal isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/645—Fungi ; Processes using fungi
- C12R2001/79—Paecilomyces
Definitions
- a novel peptide a microbiological process for its production and use thereof as an antibiotic, cytotoxic and phythotoxic agent
- the present invention relates to a novel peptide compound, a microbiological process for its production and the use thereof as an antibiotic, cytotoxic and phythotoxic agent.
- MPD methylamino-2-aminopropane Peptide compounds I and II have resulted identical with Leucinostatins A and B independently isolated by a different group of researchers from Paecilomyces lilacinus (CA, 1983, Vol. 98, 15460x).
- Fungus Paecilomyces marquandii (syn. Spicaria violacea) has been deposited at CBS (Centraalbureau voor Schimmelcutures, 3740 A6 Baarn, The Netherlands) under the deposit number CBS 141.85, dated 5 February 1985.
- An object of the present invention is a novel peptide compound of formula III
- a Further object of the present invention is a microbiological process for the production of the novel peptide, characterized in that Fungus Paecilomyces marquandii (syn. Spicaria violacea) is treated in submerged cultures, comprising: a) a first inoculation step, b) a second multiplication s t ep , c ) a t h i rd p rod u c t i on step in a sterile, aerated and pressurized environment, and d) a final step of solvent extraction of the substances so obtained and chromatographic separation for obtaining the peptide compound III.
- the third step can be carried out by using the sparger and antivortex system, or simplified vortex system, or an air-lift system.
- Solvents which can be used in the extraction step are benzene, butyl acetate, chloroform, butanol and similar solvents of fats. Benzene is particularly preferred for its higher extraction yield.
- Culture media which can be used are semisynthetic media (for example media in which the organic source is yeast autolysate) or complex organic media based upon by-products of food industry (flour from peanut and soy extraction, corn steep liquor, potato and bean broth and the like).
- a further object of the present invention is the use of the peptide as an antibiotic, cytotoxic and phythotoxic agent.
- the compound according to the present invention is obtained in a mixture with the other leucinostatins (10% of the whole) at the third step in submerged cultures: first inoculation step in flasks containing 3% potato-glucose broth at pH 6 for 5-6 days on a rotating stirrer (220 rpm) at 27°C; second multiplication step in a 5 liter Erlenmeyer flask containing 900 ml of the same medium, by incubation for three days in similar conditions; third production step in Czapek-Dox fermentors of effective 50 liters with 0.1% yeast autolysate, 3% glucose at pH 6, in conventional conditions (propeller 130 mm, 200 rpm, sparger, 3 antivortexes, 27°C, 1 atm pressure, 50 liters/min outlet air).
- the toxin extraction is generally effected on the fourth fermentation day, 24 hours after glucose exhaustion.
- the 57 signals (see Table II) which appear in the 13 C spectrum (CDCI 3 ; 50 MHz) show chemical shifts and multiplicities in accordance with the allotted structure.
- the "in vitro" antibacterial activity of the peptide compound according to the present invention was verified by carrying out a test on staphylococci recently isolated in hospital, which are resistant to some antibiotics. The results are referred in Table III. The results of additional tests on antibacterial and antimycotic activity are referred in Tables IV and V. The minimum inhibiting concentration (MIC) for determining the antibacterial and antimycotic activity was determined as follows.
- Table III compares the activity of compound III with cefazoline on different resistent staphylococci isolated in different hospitals in Lombardy (Italy)
- the cytotoxic activity of the peptide according to the present invention was evaluated on some cell Lines, such as HeLA, KB, and the results of the concentration inhibiting a 50% cell growth are referred in Table VI.
- the phythotoxic activity evaluated by the modified Gaumann test (Ann. Ist. Super. Sanita, 4, 317-332 (1968)) on Supermarmande tomato cuttings is 2 ⁇ g/ml. Said concentration produces, after a 2 days inhibition, an irreversible and progressive withering of the tested cuttings.
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Mycology (AREA)
- Botany (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT4788985 | 1985-03-28 | ||
IT47889/85A IT1199965B (it) | 1985-03-28 | 1985-03-28 | Peptide,procedimento microbiologico per la sua produzione e suo impiego come agente antibiotico,citotossico e fitotossico |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0240501A1 true EP0240501A1 (en) | 1987-10-14 |
Family
ID=11263146
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP86901996A Withdrawn EP0240501A1 (en) | 1985-03-28 | 1986-03-21 | A novel peptide, a microbiological process for its production and use theeof as an antibiotic, cytotoxic and phythotoxic agent |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0240501A1 (it) |
AU (1) | AU5662086A (it) |
IT (1) | IT1199965B (it) |
WO (1) | WO1986005791A1 (it) |
-
1985
- 1985-03-28 IT IT47889/85A patent/IT1199965B/it active
-
1986
- 1986-03-21 AU AU56620/86A patent/AU5662086A/en not_active Abandoned
- 1986-03-21 WO PCT/IT1986/000023 patent/WO1986005791A1/en unknown
- 1986-03-21 EP EP86901996A patent/EP0240501A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO8605791A1 * |
Also Published As
Publication number | Publication date |
---|---|
IT8547889A0 (it) | 1985-03-28 |
AU5662086A (en) | 1986-10-23 |
IT1199965B (it) | 1989-01-05 |
IT8547889A1 (it) | 1986-09-28 |
WO1986005791A1 (en) | 1986-10-09 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
18D | Application deemed to be withdrawn |
Effective date: 19861229 |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: CASINOVI, CARLO, GIULIO Inventor name: ROSSI, CARLO Inventor name: TUTTOBELLO, LORENZO |