DE10004667A1 - New human defensin hBD3, useful as antibacterial, antifungal and antitumor agent, particularly for control of multi-resistant pathogens - Google Patents
New human defensin hBD3, useful as antibacterial, antifungal and antitumor agent, particularly for control of multi-resistant pathogensInfo
- Publication number
- DE10004667A1 DE10004667A1 DE2000104667 DE10004667A DE10004667A1 DE 10004667 A1 DE10004667 A1 DE 10004667A1 DE 2000104667 DE2000104667 DE 2000104667 DE 10004667 A DE10004667 A DE 10004667A DE 10004667 A1 DE10004667 A1 DE 10004667A1
- Authority
- DE
- Germany
- Prior art keywords
- defensin
- antifungal
- antibacterial
- defensins
- hbd3
- 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- Withdrawn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
- 244000052769 pathogen Species 0.000 title claims abstract description 4
- 239000003242 anti bacterial agent Substances 0.000 title claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 title abstract 2
- 230000000843 anti-fungal effect Effects 0.000 title abstract 2
- 229940121375 antifungal agent Drugs 0.000 title abstract 2
- 102000000541 Defensins Human genes 0.000 title description 6
- 108010002069 Defensins Proteins 0.000 title description 6
- 239000003429 antifungal agent Substances 0.000 title 1
- 239000002246 antineoplastic agent Substances 0.000 title 1
- 102000012265 beta-defensin Human genes 0.000 claims abstract description 18
- 108050002883 beta-defensin Proteins 0.000 claims abstract description 18
- 230000003115 biocidal effect Effects 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 4
- 150000001413 amino acids Chemical class 0.000 claims abstract description 3
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 2
- 241000588722 Escherichia Species 0.000 claims description 2
- 241000589516 Pseudomonas Species 0.000 claims description 2
- 241000194017 Streptococcus Species 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical class [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000010534 mechanism of action Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 102100026887 Beta-defensin 103 Human genes 0.000 description 4
- 101000912247 Homo sapiens Beta-defensin 103 Proteins 0.000 description 4
- 244000005700 microbiome Species 0.000 description 3
- 229940126601 medicinal product Drugs 0.000 description 2
- 102100037437 Beta-defensin 1 Human genes 0.000 description 1
- 102100038326 Beta-defensin 4A Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000952040 Homo sapiens Beta-defensin 1 Proteins 0.000 description 1
- 101000884714 Homo sapiens Beta-defensin 4A Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
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
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4723—Cationic antimicrobial peptides, e.g. defensins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Gegenstand der vorliegenden Erfindung ist ein neues β-Defensin, das hBD-3, gemäß Anspruch 1, Arzneimittel enthaltend das erfindungsgemäße β-Defensin sowie Verwendung des erfindungsgemäßen β-Defensins.The present invention relates to a novel β-defensin, the hBD-3, according to claim 1, medicament containing the β-defensin according to the invention and use of the β-defensin according to the invention.
Defensine sind Polypeptide mit antibiotischer Wirkung. Aufgrund der zunehmenden Antibiotikaresistenz, insbesondere von pathogenen Mikroorganismen, ist es dringend erforderlich, das Arsenal der antibiotisch wirksamen Substanzen zu ergänzen, um diese Mikroorganismen erfolgreich zu bekämpfen. Defensine werden in Säugern in verschiedenen Geweben und Organen exprimiert.Defensins are polypeptides with an antibiotic effect. Due to the increasing resistance to antibiotics, especially pathogenic ones Microorganisms, it is imperative to keep the arsenal of antibiotic effective substances to supplement these microorganisms successfully fight. Defensins are found in mammals in various tissues and organs expressed.
Das der Erfindung zu Grunde liegende technische Problem bestand darin, weitere humane wirksame Defensine als körpereigene Abwehrstoffe (z. B. als antimokrobielle oder antitumorale Substanz) zur Verfügung zu stellen, die unter anderem als Arzneimittel beim Menschen eingesetzt werden können.The technical problem on which the invention is based consisted of further effective human defensins as the body's own antibodies (e.g. as antimocrobial or antitumor substance) to be made available under other than medicines can be used in humans.
Erfindungsgemäß gelöst wird das angesprochene technische Problem durch das
β-Defenin der Formel
Z1-CLHLQLLALKCCKI-Z2
wobei
Z1 gleich Z2 oder verschieden sind,
Z1 einen substituierten oder unsubstituierten Aminorest mit mindestens einem
weiteren Cys bedeutet,
Z2 ein Peptidrest von bis zu 20 Aminosäuren ist und mindestens zwei weitere
unmittelbar benachbarte Cys oder eine Carboxylgruppe oder eine derivatisierte
Caboxylgruppe bedeutet.
According to the invention, the technical problem addressed is solved by the β-defenin of the formula
Z 1 -CLHLQLLALKCCKI-Z 2
in which
Z 1 are the same as Z 2 or are different,
Z 1 represents a substituted or unsubstituted amino radical with at least one further Cys,
Z 2 is a peptide residue of up to 20 amino acids and means at least two further immediately adjacent Cys or a carboxyl group or a derivatized caboxyl group.
Fig. 1 zeigt einige Aminosäuresequenzen von den bekannten humanen α- Defensinen hD-1 und hD-6, sowie den β-Defensinen hBD-1 und hBD-2. Das erfindungsgemäß besonders bevorzugte Defensin ist hBD-3 (Seq ID. No 1). Fig. 1 shows some amino acid sequences of the known human defensins α- HD-1 and HD-6, as well as the β-defensins hBD-1 and hBD-2. The defensin which is particularly preferred according to the invention is hBD-3 (Seq ID. No 1).
Fig. 2 zeigt die dazugehörige cDNA Sequenz (Seq ID. No 2) des erfindungsgemäßen β-Defensins hBD3. Fig. 2 shows the corresponding cDNA sequence (SEQ ID. No 2) of the inventive β-defensin hBD3.
Die minimale Hemmkonzentration mit minimum inhibitory concentration hBD-3 gegenüber verschiedenen Mikroorganismen wurde analysiert, dabei sind Werte von 1-10 µg/ml bei verschiedenen Keimen beobachtet worden.The minimum inhibitory concentration with minimum inhibitory concentration hBD-3 against various microorganisms was analyzed, values of 1-10 µg / ml has been observed with various germs.
Das erfindungsgemäße Arzneimittel enthält also das überraschenderweise in der Leber gefundene hBD-3 als wirksamen Bestandteil, als erfindungsgemäßes β- Defensin. Dem Fachmann sind gegebenenfalls zur Formulierung der β-Defensine als Arzneimittel einsetzbare Hilfs- und Trägerstoffe geläufig. Die β-Defensine können in Mengen eingesetzt werden, die durch ihre therapeutische Breite definiert sind. Typischerweise werden sie in Mengen von 0,1 µg bis 100 mg eingesetzt.The medicinal product according to the invention surprisingly contains that in the HBD-3 found in the liver as an effective component, as a β- Defensin. The person skilled in the art may be required to formulate the β-defensins Auxiliaries and carriers that can be used as medicinal products are common. The β-defensins can be used in amounts defined by their therapeutic breadth are. They are typically used in amounts of 0.1 µg to 100 mg.
Die Formulierungen des erfindungsgemäßen β-Defensin als Lösung für intravenöse, intramuskuläre, subkultane und topische Applikationen sind bevorzugt. Das erfindungsgemäße β-Defensin insbesondere kann als antibiotisch und antitumoral wirksame Substanz eingesetzt werden. Das antibiotische Spektrum des erfindungsgemäßen β-Defensins ist weit und reich, zum Beispiel zur Behandlung von Infektionen durch multiresistente Erreger wie Streptokokkus, Bacillus, Pseudomonas, Escherichia, Staphylokokkus und Candida. The formulations of the β-defensin according to the invention as a solution for are intravenous, intramuscular, subcultaneous and topical applications prefers. The β-defensin according to the invention in particular can be considered antibiotic and antitumor active substance can be used. The antibiotic spectrum of the β-defensin according to the invention is wide and rich, for example for Treatment of infections by multi-resistant pathogens such as streptococcus, Bacillus, Pseudomonas, Escherichia, Staphylococcus and Candida.
Claims (6)
Z1-CLHLQLLALKCCKI-Z2
wobei
Z1 gleich Z2 oder verschieden sind,
Z1 einen substituierten oder unsubstituierten Aminorest mit mindestens einem weiteren Cys bedeutet,
Z2 ein Peptidrest von bis zu 20 Aminosäuren ist, und mindestens zwei weitere unmittelbar banachbarte Cys oder eine Carboxylgruppe oder derivatisierte Carboxylgruppe bedeutet.1. β-defensins of the formula
Z 1 -CLHLQLLALKCCKI-Z 2
in which
Z 1 are the same as Z 2 or are different,
Z 1 represents a substituted or unsubstituted amino radical with at least one further Cys,
Z 2 is a peptide residue of up to 20 amino acids, and means at least two further immediately adjacent Cys or a carboxyl group or derivatized carboxyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2000104667 DE10004667A1 (en) | 2000-02-03 | 2000-02-03 | New human defensin hBD3, useful as antibacterial, antifungal and antitumor agent, particularly for control of multi-resistant pathogens |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2000104667 DE10004667A1 (en) | 2000-02-03 | 2000-02-03 | New human defensin hBD3, useful as antibacterial, antifungal and antitumor agent, particularly for control of multi-resistant pathogens |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10004667A1 true DE10004667A1 (en) | 2001-08-09 |
Family
ID=7629652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2000104667 Withdrawn DE10004667A1 (en) | 2000-02-03 | 2000-02-03 | New human defensin hBD3, useful as antibacterial, antifungal and antitumor agent, particularly for control of multi-resistant pathogens |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE10004667A1 (en) |
-
2000
- 2000-02-03 DE DE2000104667 patent/DE10004667A1/en not_active Withdrawn
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |