WO2013045600A1 - Novel peptide derivatives as antibiotics - Google Patents
Novel peptide derivatives as antibiotics Download PDFInfo
- Publication number
- WO2013045600A1 WO2013045600A1 PCT/EP2012/069166 EP2012069166W WO2013045600A1 WO 2013045600 A1 WO2013045600 A1 WO 2013045600A1 EP 2012069166 W EP2012069166 W EP 2012069166W WO 2013045600 A1 WO2013045600 A1 WO 2013045600A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- xaa
- compound
- lysine
- formula
- hydroxylysine
- Prior art date
Links
- 239000003242 anti bacterial agent Substances 0.000 title description 11
- 229940088710 antibiotic agent Drugs 0.000 title description 10
- 108090000765 processed proteins & peptides Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- 230000003115 biocidal effect Effects 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
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- 239000004472 Lysine Substances 0.000 claims description 58
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 54
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- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 claims description 39
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- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 29
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- A61P31/04—Antibacterial agents
-
- 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
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- 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
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Definitions
- Xaai is lysine; Xaa 2 and Xaa 3 are each 3-hydroxy-2,4- diaminobutanoic acid; Xaa 4 is glycine; Xaa 5 is ornithine; Xaa 6 is proline; Xaa 7 is histidine; Xaagis lysine or 5-hydroxylysine; Xaa 9 is 2,3-dehydroarginine; Xaagis lysine or 5-hydroxylysine; n is 4; and R is NH 2 .
- FIG. 4 shows bactericidal effects of Odilomycin A on growing P. aeruginosa
- the present invention comprises methods of treatment, suppression and/or prevention of bacterial infection comprising administration of extracts from Xenorhabdus nematophila strain CNCM 1-4530.
- Xenorhabdus nematophila strain CNCM 1-4530 culture supernatant from this strain and cell extracts derived from this strain exhibit antibiotic activity against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Klebsiella pneumonia, Klebsiella oxytoca, Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Moraxella catarrhalis, Pseudomonas aeruginos and Stenotrophomonas maltophilia.
- n 4.
- one or more of Xaai, Xaa 2; Xaa 3 , Xaa , Xaa 5 , Xaa 6 , Xaa 7 , Xaa 8 , and Xaa ⁇ have the "D" configuration at the ⁇ -carbon of the amino acid residue.
- the configuration at the hydroxyl groups in the amino acid side chains may be "R” or "S", and may be independent of the configurations of other hydroxyl groups in the compounds of formula (I).
- one or more hydroxyl groups have the "R” configuration.
- one or more hydroxyl groups have the "S” configuration.
- each of the hydroxyl groups have the "R” configuration.
- each of the hydroxyl groups have the "S” configuration.
- compositions or methods may further comprise one or more additional antibacterial or antibiotic compounds in combination with a compound of formula (I) alone.
- additional antibacterial or antibiotic compounds include, but are not limited to, daptomycin, oxacillin, piperacillin/tazobactam, ticaricillin/clavulanic acid, amoxicillin/clavulanic acid, erythromycin, cefepim, clindamycin, imipenem, gentamicin, ciprofloxacin, aztreonam, vancomycin, linezolid, rifampicin, kanamycin, ampicillin, tetracycline, and the like.
- Another aspect of the present invention is a pharmaceutical composition comprising an effective amount of a compound of formula (I).
- Xaai is lysine.
- Xaa 5 is ornithine.
- n 4.
- the compound and/or composition is administered orally. In some embodiments, the compound and/or composition is administered subcutaneous ly. In some embodiments, the compound and/or composition is administered intravenously. In some embodiments, the compound and/or composition is administered intramuscularly. In some embodiments, the compound and/or composition is administered topically. In some embodiments, the compound and/or composition is administered parenterally.
- Odilomycin A was tested for antimicrobial activity against a wide range of bacteria involved in nosocomial and animal infection. It owns a wide spectrum of antibacterial activity against Gram-positive and Gram-negative pathogens (Table 8). With respect to Gram-positive bacteria, the antibacterial activities of Odilomycin A are strong, with MICs inferior to 1 ⁇ g/mL against S. aureus, S. epidermidis, and B. subtilis strains, including against some multiresistant clinical isolates (Table 9). Weak or no antibacterial activity was observed against E. faecalis, E. faecium, S. pneumoniae, and S. pyogenes.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201280046610.4A CN103827138B (zh) | 2011-09-28 | 2012-09-28 | 新的作为抗生素的肽衍生物 |
| ES12778971.7T ES2657930T3 (es) | 2011-09-28 | 2012-09-28 | Nuevos derivados de péptidos como antibióticos |
| JP2014532400A JP6158188B2 (ja) | 2011-09-28 | 2012-09-28 | 抗生物質としての新規なペプチド誘導体 |
| EP12778971.7A EP2760881B1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
| IN3010DEN2014 IN2014DN03010A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2011-09-28 | 2012-09-28 | |
| RU2014114996/04A RU2014114996A (ru) | 2011-09-28 | 2012-09-28 | Новые пептидные производные в качестве антибиотиков |
| US14/342,446 US9260481B2 (en) | 2011-09-28 | 2012-09-28 | Peptide derivatives as antibiotics |
| CA2845735A CA2845735A1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
| IL231664A IL231664A0 (en) | 2011-09-28 | 2014-03-23 | Novel peptide histories as antibiotics |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161540085P | 2011-09-28 | 2011-09-28 | |
| US61/540,085 | 2011-09-28 | ||
| EP11183034.5 | 2011-09-28 | ||
| EP11183034 | 2011-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2013045600A1 true WO2013045600A1 (en) | 2013-04-04 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2012/069166 WO2013045600A1 (en) | 2011-09-28 | 2012-09-28 | Novel peptide derivatives as antibiotics |
Country Status (10)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016046409A1 (en) * | 2014-09-26 | 2016-03-31 | Nosopharm | Novel peptide derivatives and uses thereof |
| WO2024200838A1 (en) * | 2023-03-31 | 2024-10-03 | Nosopharm | New odilorhabdins analogues as antibiotics against multi-resistant bacteria |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9800971B2 (en) | 2015-03-17 | 2017-10-24 | Knowles Electronics, Llc | Acoustic apparatus with side port |
| US11667674B2 (en) | 2016-04-08 | 2023-06-06 | Versitech Limited | Antibacterial cyclic lipopeptides |
| US10647746B2 (en) | 2016-04-08 | 2020-05-12 | Versitech Limited | Antibacterial cyclic lipopeptides |
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| GB2207433A (en) * | 1987-07-22 | 1989-02-01 | Nat Res Dev | Peptides |
| WO2002055545A1 (fr) * | 2001-01-12 | 2002-07-18 | Rhobio | Pseudopeptides antimicrobiens |
| WO2010136532A1 (fr) * | 2009-05-27 | 2010-12-02 | Nosopharm | Procédé pour augmenter la diversité des métabolites secondaires d'intérêt produits par des micro-organismes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110033389A1 (en) * | 2009-04-29 | 2011-02-10 | Zhifeng Chen | Modified antibodies for passive immunotherapy |
-
2012
- 2012-09-28 CN CN201280046610.4A patent/CN103827138B/zh active Active
- 2012-09-28 IN IN3010DEN2014 patent/IN2014DN03010A/en unknown
- 2012-09-28 CA CA2845735A patent/CA2845735A1/en not_active Abandoned
- 2012-09-28 JP JP2014532400A patent/JP6158188B2/ja active Active
- 2012-09-28 US US14/342,446 patent/US9260481B2/en active Active
- 2012-09-28 WO PCT/EP2012/069166 patent/WO2013045600A1/en active Application Filing
- 2012-09-28 RU RU2014114996/04A patent/RU2014114996A/ru not_active Application Discontinuation
- 2012-09-28 ES ES12778971.7T patent/ES2657930T3/es active Active
- 2012-09-28 EP EP12778971.7A patent/EP2760881B1/en active Active
-
2014
- 2014-03-23 IL IL231664A patent/IL231664A0/en unknown
Patent Citations (3)
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| GB2207433A (en) * | 1987-07-22 | 1989-02-01 | Nat Res Dev | Peptides |
| WO2002055545A1 (fr) * | 2001-01-12 | 2002-07-18 | Rhobio | Pseudopeptides antimicrobiens |
| WO2010136532A1 (fr) * | 2009-05-27 | 2010-12-02 | Nosopharm | Procédé pour augmenter la diversité des métabolites secondaires d'intérêt produits par des micro-organismes |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016046409A1 (en) * | 2014-09-26 | 2016-03-31 | Nosopharm | Novel peptide derivatives and uses thereof |
| KR20170057400A (ko) * | 2014-09-26 | 2017-05-24 | 노소팜 | 신규의 펩티드 유도체 및 그 용도 |
| JP2017533890A (ja) * | 2014-09-26 | 2017-11-16 | ノソファルムＮｏｓｏｐｈａｒｍ | 新規ペプチド誘導体およびその使用 |
| US10626144B2 (en) | 2014-09-26 | 2020-04-21 | Nosopharm | Peptide derivatives and uses thereof |
| AU2015323713B2 (en) * | 2014-09-26 | 2020-04-23 | Nosopharm | Novel peptide derivatives and uses thereof |
| JP2021100939A (ja) * | 2014-09-26 | 2021-07-08 | ノソファルムＮｏｓｏｐｈａｒｍ | 新規ペプチド誘導体およびその使用 |
| JP7123559B2 (ja) | 2014-09-26 | 2022-08-23 | ノソファルム | 新規ペプチド誘導体およびその使用 |
| KR102522224B1 (ko) * | 2014-09-26 | 2023-04-14 | 노소팜 | 신규의 펩티드 유도체 및 그 용도 |
| WO2024200838A1 (en) * | 2023-03-31 | 2024-10-03 | Nosopharm | New odilorhabdins analogues as antibiotics against multi-resistant bacteria |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2760881A1 (en) | 2014-08-06 |
| JP2014534173A (ja) | 2014-12-18 |
| ES2657930T3 (es) | 2018-03-07 |
| US9260481B2 (en) | 2016-02-16 |
| IL231664A0 (en) | 2014-05-28 |
| CN103827138B (zh) | 2016-05-25 |
| RU2014114996A (ru) | 2015-11-10 |
| US20150175659A1 (en) | 2015-06-25 |
| EP2760881B1 (en) | 2017-11-01 |
| CA2845735A1 (en) | 2013-04-04 |
| CN103827138A (zh) | 2014-05-28 |
| JP6158188B2 (ja) | 2017-07-05 |
| IN2014DN03010A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-05-08 |
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