AU2002240733A1 - Additive cytoprotective effects of two bioactive regions of pro-opiomelanocortin hormone - Google Patents
Additive cytoprotective effects of two bioactive regions of pro-opiomelanocortin hormoneInfo
- Publication number
- AU2002240733A1 AU2002240733A1 AU2002240733A AU2002240733A AU2002240733A1 AU 2002240733 A1 AU2002240733 A1 AU 2002240733A1 AU 2002240733 A AU2002240733 A AU 2002240733A AU 2002240733 A AU2002240733 A AU 2002240733A AU 2002240733 A1 AU2002240733 A1 AU 2002240733A1
- Authority
- AU
- Australia
- Prior art keywords
- komet
- pro
- bioactive
- opiomelanocortin
- combination
- 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.)
- Granted
Links
Description
"ADDITIVE CYTOPROTECTIVE EFFECTS OF TWO BIOACTIVE REGIONS OF PRO-OPIOMELANOCORTIN HORMONE"
1) TECHNICAL AREA OF THE INVENTION
The invention is a combination of two bioactive peptides extracted from the pro- opiomelanocortin hormone, that enables additive cytoprotective effects and modulation of the inflammatory response and tissue/wound healing. The combination of two pro- opiomelanocortin of peptides enables better pharmacologic effects and tissue leasion healing.
2) TECHNICAL PROBLEM
Bioactive parts of the protein and gene sequences are often 5 to 15 amino acid long and repetitive peptides, separated by the larger amino acid blocks of undefined function (1-5). Computational analyses may be used for the extraction of such motifs and subsequent manipulation with the bioactive effects their protein regions (1-5). The invention represents a combimation of two repetitive and bioactive regions of the pro- opiomelanocortin hormone that exhibits additive cytoprotective and pharmacological effects.
3) TECHNICAL DESCRIPTION
Repetitive peptide motifs within a single protein or a protein family represent, together with their matching complementary sequences, regions that are linked to the bioactivity of the larger molecular structures (1-5).
Modern programming techniques, developement of the softwares and databases of the protein and gene structures enabled the computer modelling of repetitive, bioactive and complementary structures of the large number of different proteins (1-5). Consequently, the extraction of short and repetitive motifs may be done on a personal computer quickly and easily (1-5). We analysed repetitive and bioactive peptides of the pro- opiomelanocortin molecule by means of the software SCAN (3-5) in order to obtain possible combination of elements with additive pharmacologic and cytoprotective effects.
4) PURPOSE OF THE INVENTION
The purpose of the invention is to obtain additive cytoprotective pharmacologic effects by combining two repetitive and bioactive peptides of the pro-opiomelanocortin hormone molecule.
The inovation is in the fact that, instead of the random pharmacologic screening of different pro-opiomelanocortin protein motifs, software SCAN was used to extract two repetitive and bioactive sequences (SYSMEHFRWGKPV and YGGFM). Two extracted sequences are present in the following molecules: pro-opiomelanocortin precursor, pro- opiomelanocortin, corticotropin, melanotropin, lipotropin beta, proenkephalin, preproenkephalin, endorphin beta i adrenorphin (Table 1).
Bioactive peptide fragments SYSMEHFRWGKPV and YGGFM were tested individually and in combination, by means of the standard cytoprotection model of the 96% ethanol induced gastric lesions in male Wistar rats (6, 7). In the control group of 8 animals treated with physiological saline the area of gastric lesions was 255.5+78.1 mm2 (mean ± standard deviation, Figure 1) (7). In the group of 8 animals treated with the combination of peptides SYSMEHFRWGKPV (1 mg/kg) and YGGFM (10 mg/kg) the area of gastric lesions was 0.3+0.7 mm (p < 0.05 compared to controls, Figure 1) (7). In the group of 8 animals treated with peptide SYSMEHFRWGKPV (1 mg/kg) the area of gastric lesions was 5.9 ±8 mm (p < 0.05 compared to controls, Figure 1) (7). In the group of 8 animals treated with peptide YGGFM (10 mg/kg) the area of gastric lesions was 139.4+36.1 mm2 (p < 0.05 compared to controls, Figure 1) (7). The combination of peptides SYSMEHFRWGKPV and YGGFM that provided best cytoprotective effect is patented under the name KOMET. Peptides or their combination did not show any iritative effect on the normal gastric mucosa (7).
5) FIGURES AND TABLES
Table 1 defines the combination of two bioactive sequences of pro-opiomelanocortin named KOMET, and three combinations of their chemical structural formulas KOMET-1, KOMET-2 i KOMET-3 (obtained by combining individual structural formulas).
Figure 1 defines the cytoprotective effects of the bioactive peptide fragments SYSMEHFRWGKPV and YGGFM of the pro-opiomelanocortin molecule, and their combination KOMET, in the model of the ethanol induced gastric lesions in rats.
6) DESCRIPTION OF THE POSSIBLE APPLICATIONS OF THE INVENTION Bioactive sequences KOMET, and the combination of their structural formulas KOMET- 1, KOMET-2 i KOMET-3 defined in Table 1 will be used as the bioactive peptides for the modulation of the inflammation and wound healing. The purpose of defining structural formulas KOMET, KOMET-1, KOMET-2 i KOMET-3, from the bioactive regions of the pro-opiomelanocortin hormone (6-9), is to obtain structural formulas (sequences) of the potential drugs in a quick and efficient way.
The aim of the invention KOMET, KOMET-1, KOMET-2 i KOMET-3 is to obtain the drug that prevents and stops tissue and organ damage in inflammatory and autoimmune diseases, as well as in trauma, infection and burns of the:
1. connective tissue, j oints and bones
2. central and peripheral nervous system, optic nerve, eye and ear
3. skin, hair and nails
4. digestive system, liver, pancreas, oral cavity, teeth and sinuses
5. immune system, bone marrow lymph nodes and spleen
6. cardiovascular system
7. respiratory system respiratornog sustava
8. reproductive system
6) INDUSTRIAL APPLICATIONS OF THE INVENTION
Bioactive sequences of the pro-opiomelanocortin KOMET, KOMET-1, KOMET-2 i KOMET-3 will be applied subcutaneously, intramuscularly, intraperitoneally and intravenously. Topical applications include ointments, creams, gels, suppositories, vaginal suppositories, eye-drops and ear-drops.
Claims (9)
1. Combination of the two bioactive and repetitive pro-opiomelanocortin sequences KOMET, characterised by the structural formulas SYSMEHFRWGKPV and YGGFM (Table 1), for the synthesis of drugs that are taken as systemic and topical preparations.
2. Combination of the two bioactive and repetitive pro-opiomelanocortin sequences KOMET-1, characterised by the structural formula YGGFMSYSMEHFRWGKPVYGGFM, for the synthesis of drugs that are taken as systemic and topical preparations.
3. Combination of the two bioactive and repetitive pro-opiomelanocortin sequences KOMET-2, characterised by the structural formula YGGFMSYSMEHFRWGKPV, for the synthesis of drugs that are taken as systemic and topical preparations.
4. Combination of the two bioactive and repetitive pro-opiomelanocortin sequences KOMET-3, characterised by the structural formula SYSMEHFRWGKPVYGGFM, for the synthesis of drugs that are taken as systemic and topical preparations.
REFERENCES
1. L. Baranyi, W. Campbell, K. Ohishima et al., Nature Medicine 1 (1995) 894-901.
2. J. E. Blalock, Nature Medicine, 1(1995) 876-878.
3. N. Stambuk, On the Optimization of Complementary Protein Coding, in: S. Ohno, K. Aoki, M. Usui, E. Uchio (Eds.), Uveitis Today, Elsevier, Amsterdam, 1998, pp 315-318.
4. N. Stambuk and P. Konjevoda, Period. Biol. 101 (1999) 363-368.
5. N. Stambuk, N. Goto vac, M. Martinis et al. Simple Three-step Method for the Analysis and Design of Repetitive and Bioactive protein Motifs, in: V. B. Bajic (Ed.), Advances in Systems Signals Control and Computers vol. II, IAAMSAD, and ANS, Durban, 1998, pp 310-311.
6. P. Konjevoda, N. Stambuk, D. Vikic-Topic et al. Croat. Chem. Ada 73 (2000) 1111-1121.
7. P. Konjevoda, N. Stambuk, G. Aralica and B. Pokric, J. Physiol- Paris 95 (1-6)(2001) 277-281.
8. J. M. Lipton and A. Catania, Immunol. Today 18 (1997) 140-145.
9. N. Stambuk, N. Kopjar, K. Sentija, et al. Croat. Chem. Ada 71 (1998) 591-605.
TABLES AND FIGURES
Table 1. Combination of two bioactive anf repetitive protein motifs (peptide YGGFM and peptide SYSMEHFRWGKPV) was determined computationally by means of the SCAN software (3-5) from the pro-opiomelanocortin precursor and pro-opiomelanocortin molecules. Repetitive peptid YGGFM is also present in the preproenkephalin, proenkephalin, lipotropin beta, endorphin beta and adrenorphin molecules (a). Peptide SYSMEHFRWGKPV is additionally present in melanotropin and corticotropin molecules (b).
Combination of bioactive peptides YGGFM and SYSMEHFRWGKPV of the pro- opiomelanocortin molecule is patented under the name KOMET.
Other combination of two sequences of both peptides are patented under the following names and structural formulas:
KOMET-1 characterised by the structural formula YGGFMSYSMEHFRWGKPVYGGFM, KOMET-2 characterised by the structural formula YGGFMSYSMEHFRWGKPV i KOMET-3 characterised by the structural formula SYSMEHFRWGKPVYGGFM.
(a)
Figure 1. Cytoprotective effects of the bioactive peptide fragments SYSMEHFRWGKPV and YGGFM of the pro-opiomelanocortin molekule in the rat model of the ethanol induced gastric lesions. Combination of sequences KOMET (SYSMEHFRWGKPV + YGGFM) exhibits stronger cytoprotective effects than individual peptide sequences.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BABAP01898A | 2001-10-18 | ||
BA010898 | 2001-10-18 | ||
PCT/BA2001/000005 WO2003033017A1 (en) | 2001-10-18 | 2001-11-29 | Additive cytoprotective effects of two bioactive regions of pro-opiomelanocortin hormone |
Publications (2)
Publication Number | Publication Date |
---|---|
AU2002240733A1 true AU2002240733A1 (en) | 2003-07-03 |
AU2002240733B2 AU2002240733B2 (en) | 2009-04-09 |
Family
ID=3839672
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2002240733A Ceased AU2002240733B2 (en) | 2001-10-18 | 2001-11-29 | Additive cytoprotective effects of two bioactive regions of pro-opiomelanocortin hormone |
Country Status (15)
Country | Link |
---|---|
US (1) | US7544653B2 (en) |
EP (1) | EP1435999B1 (en) |
JP (1) | JP2005508356A (en) |
CN (1) | CN1321687C (en) |
AU (1) | AU2002240733B2 (en) |
BR (1) | BR0117155A (en) |
CA (1) | CA2462713C (en) |
CY (1) | CY1114016T1 (en) |
DK (1) | DK1435999T3 (en) |
ES (1) | ES2391551T3 (en) |
MX (1) | MXPA04003504A (en) |
NO (1) | NO20042001L (en) |
PT (1) | PT1435999E (en) |
RU (1) | RU2297238C2 (en) |
WO (1) | WO2003033017A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2857588B1 (en) * | 2003-07-17 | 2007-11-30 | Oreal | USE OF BETA-ENDORPHINE, AGENTS EXERCISING BETA-ENDORPHINE-LIKE ACTIVITY IN COSMETICS AND DERMATOLOGY |
AU2011265315B2 (en) * | 2004-05-12 | 2014-08-28 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods related to the treatment of neurodegenerative and inflammatory conditions |
WO2010054446A1 (en) | 2008-11-11 | 2010-05-20 | Ademovic Zlatko | Combination of two or more peptides in a single stable lyophilized pharmaceutical compound |
WO2015033175A1 (en) | 2013-09-06 | 2015-03-12 | Zlatko Ademovic | Combination of pro-opiomelanocortin endogenous peptides in autoimmune disease treatment |
US10644009B2 (en) | 2017-12-21 | 2020-05-05 | Renesas Electronics Corporation | Semiconductor memory device |
CN109824772B (en) * | 2019-02-28 | 2022-07-29 | 海南大学 | Gene recombination human corticotropin precursor for improving serum glucocorticoid level and preparation method thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69836386T2 (en) * | 1997-08-22 | 2007-10-11 | Kaken Pharmaceutical Co., Ltd. | Amides to promote the secretion of growth hormones |
WO2000004873A1 (en) * | 1998-07-22 | 2000-02-03 | Smith & Nephew Plc | Dermatological compositions for the treatment of scars |
CA2499211A1 (en) * | 1999-05-17 | 2000-11-23 | Conjuchem Inc. | Modified peptides yy and conjugates thereof |
-
2001
- 2001-11-29 AU AU2002240733A patent/AU2002240733B2/en not_active Ceased
- 2001-11-29 MX MXPA04003504A patent/MXPA04003504A/en not_active Application Discontinuation
- 2001-11-29 CA CA2462713A patent/CA2462713C/en not_active Expired - Fee Related
- 2001-11-29 EP EP01988010A patent/EP1435999B1/en not_active Expired - Lifetime
- 2001-11-29 DK DK01988010.3T patent/DK1435999T3/en active
- 2001-11-29 PT PT01988010T patent/PT1435999E/en unknown
- 2001-11-29 JP JP2003535819A patent/JP2005508356A/en active Pending
- 2001-11-29 BR BR0117155-0A patent/BR0117155A/en not_active Application Discontinuation
- 2001-11-29 WO PCT/BA2001/000005 patent/WO2003033017A1/en active Application Filing
- 2001-11-29 RU RU2004114992/15A patent/RU2297238C2/en active
- 2001-11-29 US US10/492,908 patent/US7544653B2/en not_active Expired - Lifetime
- 2001-11-29 CN CNB01823710XA patent/CN1321687C/en not_active Expired - Fee Related
- 2001-11-29 ES ES01988010T patent/ES2391551T3/en not_active Expired - Lifetime
-
2004
- 2004-05-14 NO NO20042001A patent/NO20042001L/en not_active Application Discontinuation
-
2012
- 2012-10-12 CY CY20121100950T patent/CY1114016T1/en unknown
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