WO2003082906A2 - Neurotrophe und neuroprotektive peptide - Google Patents
Neurotrophe und neuroprotektive peptide Download PDFInfo
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- WO2003082906A2 WO2003082906A2 PCT/AT2003/000065 AT0300065W WO03082906A2 WO 2003082906 A2 WO2003082906 A2 WO 2003082906A2 AT 0300065 W AT0300065 W AT 0300065W WO 03082906 A2 WO03082906 A2 WO 03082906A2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0819—Tripeptides with the first amino acid being acidic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1021—Tetrapeptides with the first amino acid being acidic
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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
Definitions
- the present invention relates to peptides of 4 to 14 amino acids in length.
- the peptides according to the invention can be used as active ingredients in medicaments for the treatment of degenerative diseases of the central nervous system, such as Alzheimer's disease, Lewy body dementia, Parkinson's disease, Huntington's disease (chorea), multisystem atrophy and other similar diseases.
- degenerative diseases of the central nervous system such as Alzheimer's disease, Lewy body dementia, Parkinson's disease, Huntington's disease (chorea), multisystem atrophy and other similar diseases.
- Alzheimer's disease In neurodegenerative diseases, aggregates of proteins in the brain generally appear as a common feature. In the case of Alzheimer's disease, it is the so-called senile plaques, extracellular protein deposits, which consist primarily of amyloid beta peptides, and the so-called neurofibrillary tangles, intracellular protein knuckles made of hyperphosphorylated tau protein. In Parkinson's disease there are intracellular emptying bodies consisting of aggregated alpha-synuclein. According to the latest scientific findings, such bodies, namely Lewy Bodies, were also found in more than 70% of familial and sporadic Alzheimer's sufferers, and they can also be found in patients suffering from Down syndrome.
- Some of the sufferers have mutated proteins that have a particularly pronounced aggregation behavior. In the majority of patients, however, the aggregates consist of normal wild-type proteins. Various causes are assumed which suddenly change the solubility behavior of the proteins, whereby, for example, increased oxidative stress could play an important role during the aging process. Changes in the capacity of various protein-degrading enzymes can also be considered as a cause, since malfunctions can result in incorrectly modified proteins, which are then deposited and can no longer be processed by different disposal enzymes.
- Another triggering pathophysiological mechanism consists in a disturbed balance between aggregatic and anti-aggregate proteins.
- other representatives of this protein family include gamma-synuclem and beta-synuclem, as well as the recently discovered synoretin (Surgurchov et al., Mol. Cell. Neurosci. 13 (2): 95-103 [1999]).
- beta-synuclein a very close relative of alpha-synuclein, is able to inhibit the aggregation of alpha-synuclein in a dose-dependent manner (Hashimoto et al., Neuron 32 (2): 213- 23 [2001]).
- Experiments in cell cultures in which a disturbance in normal cell proliferation and differentiation was triggered by overexpression of alpha-synuclem also showed a therapeutic effect of beta-synuclein, which normalized the attachment, survival and outgrowth of neurites in these cultures.
- mice that are transgenic for alpha-synuclem show an increased production of this protein and therefore have a disturbed ratio in the amounts between alpha and beta-synuclein. Over the course of their age, they form intraneuronal embryos similar to the Lewy Bodies and also show progressive motor disorders that are comparable to the functional disorder in Parkinson's disease. If these animals are crossed with beta-synuclein transgenic animals which show an increased expression of this protein, homeostasis can be restored at a much higher level in the total expression of the synucleins. As a result, the number of emptying bodies is reduced significantly and the characteristic loss of neuronal function is completely prevented.
- Alpha-Synuclem was also allowed to play a particularly important role in the pathology of Alzheimer's disease. This is supported by the fact that a part of this protein, the NACP (non-amyloid component protein) domain, could be detected as part of the senile plaques (Yoshimoto et al., Proc. Natl. Acad. Sei 92, 9141-5 [1995 ] and WO-9506407), and also the fact that - as mentioned above - about 70% of Alzheimer's sufferers have Lewy Bodies in various areas of the brain, which also contain alpha-synuclein (Eizo et al., Neurosci. Lett. 290 (1), 41-4 [2000]).
- beta-amyloid increases the accumulation and neurotoxicity of alpha-synuclein (Masliah et al., Proc. Natl. Acad. Sci 98 (21): 12245-50 [2001]).
- alpha-synuclein as a synaptic protein could play an important role in the initial synaptic degeneration and thus play a key role in the pathogenesis.
- beta-synuclein and in particular peptides derived therefrom in connection with alpha-synuclein is known, see, for example, octapeptides according to WO-A-02/04482 and three others
- WO-A-002/0020 and WO-A-01/60794 describe the use of beta-synuclein as a whole molecule or of methods which increase its expression in vivo for the therapy of neurological diseases associated with alpha-synuclein
- WO-A-01/60794 does not provide any Evidence of an actual protective effect of this peptide on living, neuronal cells and contains no evidence of other effective peptides in this sequence region.
- shorter peptides were very advantageous for use as pharmaceuticals, since the problems of chemical and biological stability and bioavailability generally decrease significantly with decreasing chain length.
- the object of the present invention is to avoid the disadvantages known from the prior art.
- peptides are proposed which are from the group
- peptides according to the invention are derived from the N-terminal sequence of the beta synuclein and antagonize the influence of toxic or vitality-damaging noxae, such as are present in neurodegenerative diseases.
- peptides whose individual components are L-amino acids, but also peptides whose individual components are D-amino acids are within the scope of the invention. Also considered in the context of the invention are N- or C-terminally modified peptides.
- the invention further relates to medicaments which contain the peptides according to the invention as active pharmaceutical ingredients.
- the peptides of the invention can be synthesized in a variety of ways.
- Chemical synthesis of a peptide is a conventional process and can be achieved, for example, by the Memfield solid phase synthesis technique (Memfield, J., Am. Ch ⁇ m. Soc, 85: 2149-2154 [1963]; Kent et al., Syntheti c Pepti des n Bi ology and Medi ane, 29 ff eds.Alitalo et al., Elsevier Science Publishers 1985; Haug, JD Peptide Synthesis and the protecting group strategy, Ameri can Bi otechnology Laboratory, 5 (1): 40-47 [1987 ]).
- Chemical peptide synthesis methods also include the use of automated peptide synthesizers using commercially available protected amino acids such as Biosearch (Model 9500 and 9600), Applied Biosystems Inc. (Model 430; Miligen (Model 9050) and others.
- these can Peptides are produced in cells of bacteria, fungi or mammals using recombinant technology and purified using conventional methods.
- Cysteinyl residues can also be obtained by reaction with bromot ⁇ fluoroacetone, alpha-bromo-beta (5-imidozoyl) propionic acid, chloroacetyl-phosphate, N-alkylmalemides, 3-nitro2-pyridyldisulfide, methyl-2-pyridyldi-sulfide, p-chloromerkuribenzo Chloromeric 4-nitrophenol or chloro-7-nitrobenzo-2-oxa-1,3-diazole are de-vatized.
- amino acid histidm can also be easily derivatized by reaction with diethylprocarbonate at a pH of 5.5 - 7, as this substance is relatively specific for the histidyl side chain.
- Parabromophenacyl bromide is also an option, the reaction preferably being carried out in 0.1 molar sodium cacodylate at pH 6.0.
- Lys and amino terminal residues can also be derivatized with succinate or other carboxylic acid anhydrides.
- the reaction with these agents has the effect of reversing the charge on the lysinyl residue.
- suitable reagents for the derivatization of residues containing alphaammo include imido esters such as methyl bicolinimidate, py ⁇ doxal phosphate, py ⁇ doxal, chloroborohyd ⁇ d, trinitrobenzenesulfonic acid, O-methyl isourea, 2, 4 pentanedione and transaminase-catalyzed reactions with glyoxylate.
- the arginyl residues can be modified by the reaction with one or more conventional reagents such as phenylglyoxal, 2,3-butanedione, 1,2-cyclohexanedione and ninhydrin.
- the derivatization of the arginyl residues requires that the reaction be carried out under alkaline conditions because of the high PK value of the guanidine group.
- these reagents can also react with groups of the Lysm, as well as with the Arginine-Epsilon Ammo group.
- Tyrosyl residues are known targets for the introduction of spectral labels by the reaction with aromatic diazonium substances or tetranitromethane.
- aromatic diazonium substances or tetranitromethane Most commonly, N-acetylimidizole and tetranitromethane are used to make O-acetyltyrosil and 3- To produce nitroderivatives.
- Such derivatizations can serve to improve solubility, absorption, biological half-life and the like. Alternatively, the derivatizations could also serve to minimize any undesired side effects of the proteins.
- one day old, fertilized chicken eggs are incubated at +12 +/- 0.1 ° C and 80 +/- 5% humidity for eight days.
- the eggs are transferred to an incubation incubator and incubated until embryonic day 8 at 38 +/- 0, 5 ° C and 55 +/- 5%.
- the cortices are isolated, homogenized and neurons taken into primary culture (culture conditions: Dulbecco's Modified Eagle's Medium, 20% v / v fetal calf serum, 0.01% gentamycin, 1 g / 1 glucose, 2 mM L-glutamate, + 37 ° C, 5% C0 2 and 95% humidity).
- the peptide to be tested is added (final concentrations from 1.56 to 200 ⁇ M) and the specified noxa is carried out. A damaged control and a vehicle control are carried out with each attempt. After the specified stress period has elapsed, the proportion of neurons still alive is determined using a metabolic colorimetric assay (the yellow chromophore MTT is only converted to a blue formazan product by living cells).
- Example 2 Chronic calcium metabolism disorder caused by ionomycin It is believed that various neurodegenerative diseases result in chronic calcium overload due to metabolic malfunctions, which ultimately causes cell death through the activation of various enzyme systems. In the present model, this damage is induced by adding ionomycin in a methanolic solution (final concentration: 10 ⁇ M) over a period of 24 hours. Methanol, diluted in medium, serves as a vehicle control.
- Beta-amyloid - peptides in aggregate form represent a potent neurotoxin, the addition of which to nerve cell cultures leads to rapid and progressive cell death. Since beta-amyloid peptides play an essential role in the pathogenesis of Alzheimer's disease, this model is to be regarded as particularly relevant.
- the present biological test is a method for testing anti-aggregatory substance potential specially developed for this project.
- the newly synthesized peptides are added directly to a fresh solution of amyloid beta peptides to prevent the formation of neurotoxic aggregates.
- the effect of aggregates that still arise on the growth and survival of nerve cell cultures is the measurement parameter.
- ß-A beta-amyloid peptide
- phosphate-buffered cooking acid 1 mM
- this solution is pipetted into the cultures at a final concentration of 20 ⁇ M and, after 24 hours of exposure, the proportion of living cells is determined as usual.
- the compounds of the invention m therapeutically effective amounts administered in pharmaceutically acceptable carriers or solvents.
- Such carriers include (but are not limited to) physiological saline, buffered saline, dextrose, water, glycine, ethanol, and combinations thereof.
- the respective formulation should be adapted to the type of administration.
- the composition can also contain different amounts of moisturizers or emulsifiers or pH-buffering substances.
- the pharmaceutical composition can be a liquid solution, a suspension, an emulsion, a tablet, a pill, a capsule, a sustained-release formulation or a powder.
- the preparation can also be produced as a supplement with traditional binders and carriers such as triglycerides.
- Oral formulations can contain standard carriers such as mannitol, lactose, starch, magnesium sterate, sodium sacarin, cellulose, magnesium carbonate and others of pharmaceutical grade.
- Various administration systems are known and can be used to ensure the therapeutic use of the substances according to the invention, e.g. encapsulation in liposomes, microparticles, microcapsules etc.
- the dosage form is prepared in accordance with routine procedures as a pharmaceutical dosage form adapted for intravenous administration to humans or other mammals.
- the compositions for intravenous administration are solutions in sterile isotonic aqueous buffer solution. If necessary, the preparation can also contain solubilizers and locally effective anesthetics to relieve the pain at the injection site.
- the ingredients are either provided separately or mixed in a unit dose.
- a dry lyophilized powder or anhydrous concentrate in a hermetically sealed container such as an ampoule, on which the amount of the active pharmaceutical is noted.
- the dosage form has to be administered as an infusion, it can be dissolved in an infusion bottle containing sterile water or saline solution of pharmaceutical grade. Whenever the preparation is given by injection, one can Ampoules with sterile water for injections or saline are made available in such a way that the individual components can be mixed correctly before administration.
- the therapeutic substances described in the invention can be formulated both as a neutral form and as a salt.
- Pharmaceutically acceptable salts include those formed with the free amino groups, e.g. those derived from hydrochloric acid or oxalic acid and those formed with free carboxyl groups such as those derived from sodium, potassium, ammonium, calcium, iron oxides, isopropylamine, triethylamm, 2-ethyloaminoethanol, histidine, procaine and others.
- the amount of therapeutic agent described in the invention must be effective for the treatment of the particular disease or condition, will depend on the nature of the disease or condition, and will be determined by standardized clinical procedures.
- the exact dose to be used in the invention also depends on the mode of administration and the severity of the disease or disorder, and this amount should be adjusted according to the experienced physician, taking into account the specific patient circumstances.
- Suitable dosage ranges for intravenous administration are generally between 20-4,000 ⁇ g of the active ingredient per kg of body weight.
- Suitable dosages for intranasal applications range from 0.01 pg per kg body weight to 1 mg per kg body weight.
- Effective dosages for oral applications are in the range of 1 mg to 1,000 mg per kg body weight and day.
- the effective doses are extrapolated from dose-response curves derived from in vitro models or animal model test systems.
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Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002480633A CA2480633A1 (en) | 2002-03-28 | 2003-03-10 | Neurotrophic and neuroprotective peptides |
AU2003212074A AU2003212074A1 (en) | 2002-03-28 | 2003-03-10 | Neurotrophic and neuroprotective peptides |
EP03707885A EP1499636A2 (de) | 2002-03-28 | 2003-03-10 | Neurotrophe und neuroprotektive peptide |
JP2003580370A JP2006508022A (ja) | 2002-03-28 | 2003-03-10 | 神経栄養性および神経保護性ペプチド |
NZ535623A NZ535623A (en) | 2002-03-28 | 2003-03-10 | Peptides, 4-14 amino acids in length, for treating degenerative conditions of the CNS |
US10/509,095 US20060036073A1 (en) | 2002-03-28 | 2003-03-10 | Neurotrophic and neuroprotective peptides |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT0049502A AT500282A3 (de) | 2002-03-28 | 2002-03-28 | Neurotrophe und neuroprotektive peptide |
ATA495/2002 | 2002-03-28 |
Publications (2)
Publication Number | Publication Date |
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WO2003082906A2 true WO2003082906A2 (de) | 2003-10-09 |
WO2003082906A3 WO2003082906A3 (de) | 2004-11-25 |
Family
ID=28458152
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/AT2003/000065 WO2003082906A2 (de) | 2002-03-28 | 2003-03-10 | Neurotrophe und neuroprotektive peptide |
Country Status (8)
Country | Link |
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US (1) | US20060036073A1 (de) |
EP (1) | EP1499636A2 (de) |
JP (1) | JP2006508022A (de) |
AT (1) | AT500282A3 (de) |
AU (1) | AU2003212074A1 (de) |
CA (1) | CA2480633A1 (de) |
NZ (1) | NZ535623A (de) |
WO (1) | WO2003082906A2 (de) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007126111A1 (ja) * | 2006-04-28 | 2007-11-08 | Kagoshima University | アミロイドβ線維化阻害ペプチド |
JP2008505077A (ja) * | 2004-06-29 | 2008-02-21 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | Fkbp結合組成物及びその医薬上の使用 |
US7915220B2 (en) * | 2006-12-06 | 2011-03-29 | Jsw-Research Forschungslabor Gmbh | Peptidomimetic agents from dextrorotatory amino acids as well as pharmaceutical agents that contain the latter for treatment of neurodegenerative diseases |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUE028729T2 (en) | 2009-03-09 | 2017-01-30 | Ramot At Tel-Aviv Univ Ltd | Compositions for the prevention and treatment of neurodegenerative diseases |
JP5664992B2 (ja) * | 2009-08-26 | 2015-02-04 | 国立大学法人名古屋大学 | 細胞特異的ペプチド及びその用途 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0182356A2 (de) * | 1984-11-19 | 1986-05-28 | The Montefiore Hospital Association of Western Pennsylvania | Nährstoffzusammensetzungen |
WO2000020020A2 (en) * | 1998-10-06 | 2000-04-13 | The Regents Of The University Of California | Method for screening for anti-amyloidogenic properties and method for treatment of neurodegenerative disease |
WO2001060794A2 (en) * | 2000-02-18 | 2001-08-23 | The Regents Of The University Of California | Method for screening for anti-amyloidogenic properties and method for treatment of neurodegenerative disease |
WO2002004482A1 (en) * | 2000-07-07 | 2002-01-17 | Panacea Pharmaceuticals, Inc. | Methods for preventing neural tissue damage and for the treatment of alpha-synuclein diseases |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2311201A1 (en) * | 1999-08-05 | 2001-02-05 | Genset S.A. | Ests and encoded human proteins |
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2002
- 2002-03-28 AT AT0049502A patent/AT500282A3/de not_active Application Discontinuation
-
2003
- 2003-03-10 US US10/509,095 patent/US20060036073A1/en not_active Abandoned
- 2003-03-10 AU AU2003212074A patent/AU2003212074A1/en not_active Abandoned
- 2003-03-10 EP EP03707885A patent/EP1499636A2/de not_active Withdrawn
- 2003-03-10 JP JP2003580370A patent/JP2006508022A/ja active Pending
- 2003-03-10 WO PCT/AT2003/000065 patent/WO2003082906A2/de not_active Application Discontinuation
- 2003-03-10 CA CA002480633A patent/CA2480633A1/en not_active Abandoned
- 2003-03-10 NZ NZ535623A patent/NZ535623A/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0182356A2 (de) * | 1984-11-19 | 1986-05-28 | The Montefiore Hospital Association of Western Pennsylvania | Nährstoffzusammensetzungen |
WO2000020020A2 (en) * | 1998-10-06 | 2000-04-13 | The Regents Of The University Of California | Method for screening for anti-amyloidogenic properties and method for treatment of neurodegenerative disease |
WO2001060794A2 (en) * | 2000-02-18 | 2001-08-23 | The Regents Of The University Of California | Method for screening for anti-amyloidogenic properties and method for treatment of neurodegenerative disease |
WO2002004482A1 (en) * | 2000-07-07 | 2002-01-17 | Panacea Pharmaceuticals, Inc. | Methods for preventing neural tissue damage and for the treatment of alpha-synuclein diseases |
Non-Patent Citations (6)
Title |
---|
BAROOSHIAN A V ET AL: "Thin-layer chromatographic determination of the optical purity of labeled amino acids via dipeptide formation." ANALYTICAL BIOCHEMISTRY. OCT 1972, Bd. 49, Nr. 2, Oktober 1972 (1972-10), Seiten 602-606, XP002294070 ISSN: 0003-2697 * |
BUCHT G ET AL: "Optimising the signal peptide for glycosyl phosphatidylinositol modification of human acetylcholinesterase using mutational analysis and peptide-quantitative structure-activity relationships." BIOCHIMICA ET BIOPHYSICA ACTA. 18 MAY 1999, Bd. 1431, Nr. 2, 18. Mai 1999 (1999-05-18), Seiten 471-482, XP002294071 ISSN: 0006-3002 * |
GUENTHER K ET AL: "THIN-LAYER CHROMATOGRAPHIC SEPARATION OF STEREOISOMERIC DIPEPTIDES" ANGEWANDTE CHEMIE INTERNATIONAL EDITION IN ENGLISH, Bd. 25, Nr. 3, 1986, Seiten 278-279, XP002294072 ISSN: 0570-0833 * |
HASHIMOTO M ET AL: "OXIDATIVE STRESS INDUCES AMYLOID-LIKE AGGREGATE FORMATION OF NACP/ALPHA-SYNUCLEIC IN VITRO" NEUROREPORT, RAPID COMMUNICATIONS OF OXFORD, OXFORD, GB, Bd. 10, Nr. 4, 17. März 1999 (1999-03-17), Seiten 717-721, XP000891964 ISSN: 0959-4965 * |
IWAI, AKIHIKO ET AL: "Precursor protein of non-A.beta. component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system" NEURON , 14(2), 467-75 CODEN: NERNET; ISSN: 0896-6273, 1995, XP002294068 * |
LEFTHERIS, K. ET AL: "Peptide based P21ras farnesyl transferase inhibitors: systematic modification of the tetrapeptide CA1A2X motif" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS , 4(7), 887-92 CODEN: BMCLE8; ISSN: 0960-894X, 1994, XP002294069 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2008505077A (ja) * | 2004-06-29 | 2008-02-21 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | Fkbp結合組成物及びその医薬上の使用 |
JP4812758B2 (ja) * | 2004-06-29 | 2011-11-09 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | Fkbp結合組成物及びその医薬上の使用 |
WO2007126111A1 (ja) * | 2006-04-28 | 2007-11-08 | Kagoshima University | アミロイドβ線維化阻害ペプチド |
US8101578B2 (en) | 2006-04-28 | 2012-01-24 | Kagoshima University | Amyloid [β] Beta fibrillogenesis-inhibiting peptide |
JP5190957B2 (ja) * | 2006-04-28 | 2013-04-24 | 国立大学法人 鹿児島大学 | アミロイドβ線維化阻害ペプチド |
US8697651B2 (en) | 2006-04-28 | 2014-04-15 | Kagoshima University | Amyloid β fibrillogenesis-inhibiting peptide |
US7915220B2 (en) * | 2006-12-06 | 2011-03-29 | Jsw-Research Forschungslabor Gmbh | Peptidomimetic agents from dextrorotatory amino acids as well as pharmaceutical agents that contain the latter for treatment of neurodegenerative diseases |
Also Published As
Publication number | Publication date |
---|---|
AU2003212074A1 (en) | 2003-10-13 |
CA2480633A1 (en) | 2003-10-09 |
US20060036073A1 (en) | 2006-02-16 |
NZ535623A (en) | 2007-03-30 |
JP2006508022A (ja) | 2006-03-09 |
AT500282A3 (de) | 2006-06-15 |
AT500282A2 (de) | 2005-11-15 |
WO2003082906A3 (de) | 2004-11-25 |
EP1499636A2 (de) | 2005-01-26 |
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