CA2933405A1 - Protease-resistant peptides - Google Patents
Protease-resistant peptides Download PDFInfo
- Publication number
- CA2933405A1 CA2933405A1 CA2933405A CA2933405A CA2933405A1 CA 2933405 A1 CA2933405 A1 CA 2933405A1 CA 2933405 A CA2933405 A CA 2933405A CA 2933405 A CA2933405 A CA 2933405A CA 2933405 A1 CA2933405 A1 CA 2933405A1
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- alpha
- phe
- methyl
- synthetic
- 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.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 281
- 108091005804 Peptidases Proteins 0.000 title claims abstract description 26
- 239000004365 Protease Substances 0.000 title claims abstract description 25
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 130
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title abstract 4
- 150000001413 amino acids Chemical class 0.000 claims abstract description 158
- 238000000034 method Methods 0.000 claims abstract description 85
- HYOWVAAEQCNGLE-JTQLQIEISA-N alpha-methyl-L-phenylalanine Chemical compound OC(=O)[C@](N)(C)CC1=CC=CC=C1 HYOWVAAEQCNGLE-JTQLQIEISA-N 0.000 claims abstract description 20
- 235000001014 amino acid Nutrition 0.000 claims description 158
- 229940024606 amino acid Drugs 0.000 claims description 157
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 claims description 90
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 claims description 51
- 238000006467 substitution reaction Methods 0.000 claims description 47
- 108090000631 Trypsin Proteins 0.000 claims description 37
- 102000004142 Trypsin Human genes 0.000 claims description 37
- 125000000539 amino acid group Chemical group 0.000 claims description 37
- 239000012588 trypsin Substances 0.000 claims description 37
- 102000003729 Neprilysin Human genes 0.000 claims description 35
- 108090000028 Neprilysin Proteins 0.000 claims description 35
- 229960002376 chymotrypsin Drugs 0.000 claims description 33
- 230000017854 proteolysis Effects 0.000 claims description 32
- 108090000317 Chymotrypsin Proteins 0.000 claims description 31
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- 229940111202 pepsin Drugs 0.000 claims description 24
- 102000035195 Peptidases Human genes 0.000 claims description 22
- 230000015556 catabolic process Effects 0.000 claims description 22
- 238000006731 degradation reaction Methods 0.000 claims description 20
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 19
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- 102000057297 Pepsin A Human genes 0.000 claims description 18
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- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims description 13
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- MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 claims description 12
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 claims description 11
- 230000002255 enzymatic effect Effects 0.000 claims description 11
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 claims description 11
- 230000029226 lipidation Effects 0.000 claims description 11
- 108010088842 Fibrinolysin Proteins 0.000 claims description 10
- 108010067372 Pancreatic elastase Proteins 0.000 claims description 10
- 102000016387 Pancreatic elastase Human genes 0.000 claims description 10
- 108090000190 Thrombin Proteins 0.000 claims description 10
- 229940012957 plasmin Drugs 0.000 claims description 10
- 229960004072 thrombin Drugs 0.000 claims description 10
- 102000004877 Insulin Human genes 0.000 claims description 9
- 108090001061 Insulin Proteins 0.000 claims description 9
- 229940125396 insulin Drugs 0.000 claims description 9
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims description 9
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- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 7
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- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 claims description 7
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- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 7
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- C—CHEMISTRY; METALLURGY
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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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
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- C07K14/575—Hormones
- C07K14/605—Glucagons
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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Landscapes
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- Analytical Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361915662P | 2013-12-13 | 2013-12-13 | |
| US61/915,662 | 2013-12-13 | ||
| PCT/EP2014/077240 WO2015086686A2 (en) | 2013-12-13 | 2014-12-10 | Protease resistant peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2933405A1 true CA2933405A1 (en) | 2015-06-18 |
Family
ID=52021207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2933405A Abandoned CA2933405A1 (en) | 2013-12-13 | 2014-12-10 | Protease-resistant peptides |
Country Status (11)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI726889B (zh) | 2015-06-10 | 2021-05-11 | 英商梅迪繆思有限公司 | 蛋白酶抗性之脂化肽 |
| EP3368556B1 (en) * | 2015-10-28 | 2024-04-10 | Tufts University | Novel polypeptides with improved proteolytic stability, and methods of preparing and using same |
| JP2019525732A (ja) | 2016-06-09 | 2019-09-12 | メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ | プロテアーゼ耐性一脂質付加ペプチド |
| EP3681900A4 (en) | 2017-09-11 | 2021-09-08 | Protagonist Therapeutics, Inc. | OPIOID AGONIST PEPTIDES AND THEIR USES |
| MY202560A (en) | 2018-04-05 | 2024-05-08 | Sun Pharmaceutical Ind Ltd | Novel glp-1 analogues |
| WO2021198229A1 (en) * | 2020-03-31 | 2021-10-07 | Antaros Medical Ab | Selective gip receptor agonists comprising a chelating moiety for imaging and therapy purposes |
| US20240067693A1 (en) * | 2020-12-16 | 2024-02-29 | Medimmune Limited | Polypeptides and uses thereof |
| TW202346323A (zh) * | 2022-02-07 | 2023-12-01 | 英商梅迪繆思有限公司 | 具有改善的生物穩定性的ｇｌｐ—１及升糖素雙重激動肽 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL202367B1 (pl) * | 1998-12-07 | 2009-06-30 | Sod Conseils Rech Applic | Związki stanowiące analogi GLP-1, kompozycje zawierające te związki oraz zastosowanie tych związków |
| CA2641053A1 (en) * | 2006-02-08 | 2007-08-16 | Lonza Ag | Synthesis of glucagon-like peptide |
| US20100022457A1 (en) * | 2006-05-26 | 2010-01-28 | Bristol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| US20090318353A1 (en) * | 2006-08-25 | 2009-12-24 | Novo Nordisk A/S | Acylated Exendin-4 Compounds |
| PT2231701E (pt) * | 2007-12-11 | 2012-05-28 | Cadila Healthcare Ltd | Peptidomiméticos com actividades antagonistas do glucagon e agonistas do glp-1 |
| ES2354488T3 (es) * | 2008-04-18 | 2011-03-15 | F. Hoffmann-La Roche Ag | Alfa-n-metilación de aminoácidos. |
| WO2011048614A2 (en) * | 2009-10-22 | 2011-04-28 | Cadila Healthcare Limited | Short chain peptidomimetics based orally active glp-1 agonist and glucagon receptor antagonist |
| US20130143800A1 (en) * | 2011-11-07 | 2013-06-06 | Research Development Foundation | Combination therapies to treat diabetes |
| WO2014049610A2 (en) * | 2012-09-26 | 2014-04-03 | Cadila Healthcare Limited | Peptides as gip, glp-1 and glucagon receptors triple-agonist |
| WO2014088631A1 (en) * | 2012-12-06 | 2014-06-12 | Stealth Peptides International, Inc. | Peptide therapeutics and methods for using same |
-
2014
- 2014-12-10 CA CA2933405A patent/CA2933405A1/en not_active Abandoned
- 2014-12-10 AU AU2014363547A patent/AU2014363547A1/en not_active Abandoned
- 2014-12-10 JP JP2016538037A patent/JP2017502003A/ja active Pending
- 2014-12-10 EP EP14809857.7A patent/EP3080153A2/en not_active Withdrawn
- 2014-12-10 SG SG10201805039UA patent/SG10201805039UA/en unknown
- 2014-12-10 BR BR112016013157A patent/BR112016013157A2/pt not_active Application Discontinuation
- 2014-12-10 EP EP18182275.0A patent/EP3415526A1/en not_active Withdrawn
- 2014-12-10 MX MX2016007407A patent/MX2016007407A/es unknown
- 2014-12-10 KR KR1020167018887A patent/KR20160098406A/ko not_active Withdrawn
- 2014-12-10 WO PCT/EP2014/077240 patent/WO2015086686A2/en not_active Ceased
- 2014-12-10 US US15/103,607 patent/US20160318987A1/en not_active Abandoned
- 2014-12-10 CN CN201480067307.1A patent/CN105849123A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2015086686A3 (en) | 2015-10-29 |
| MX2016007407A (es) | 2016-12-12 |
| SG10201805039UA (en) | 2018-07-30 |
| AU2014363547A1 (en) | 2016-06-30 |
| CN105849123A (zh) | 2016-08-10 |
| WO2015086686A2 (en) | 2015-06-18 |
| EP3080153A2 (en) | 2016-10-19 |
| US20160318987A1 (en) | 2016-11-03 |
| JP2017502003A (ja) | 2017-01-19 |
| BR112016013157A2 (pt) | 2017-09-26 |
| EP3415526A1 (en) | 2018-12-19 |
| KR20160098406A (ko) | 2016-08-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20210302 |