JP5607176B2 - 新規ペプチドおよびその用途 - Google Patents
新規ペプチドおよびその用途 Download PDFInfo
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- JP5607176B2 JP5607176B2 JP2012544408A JP2012544408A JP5607176B2 JP 5607176 B2 JP5607176 B2 JP 5607176B2 JP 2012544408 A JP2012544408 A JP 2012544408A JP 2012544408 A JP2012544408 A JP 2012544408A JP 5607176 B2 JP5607176 B2 JP 5607176B2
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- 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
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1841—Transforming growth factor [TGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
前記式で、X1はGluまたはAspであり、X2はHis、LysまたはArgであり、X3はAspまたはGluであり、前記Gluはグルタミン酸、Aspはアスパラギン酸、Leuはロイシン、Hisはヒスチジン、LysはリシンでArgはアルギニンである。
ペプチドの製造
配列番号1のアミノ酸配列を有するペプチド(Glu−Leu−His−Leu−Asp:配列番号1)を(株)ペプトロン(Peptron Inc)(韓国)に依頼して製造した。具体的に自動合成器(ASP48S、Peptron Inc)を使用してFmoc SPPS(9−Fluorenylmethyloxycarbonyl solid phase peptide synthesis)方法を利用してC−末端から一つずつカップリング(coupling)した。
ペプチドの製造
実施例1のアミノ酸配列の代わりに、下記の表1に記載されたアミノ酸配列としたものを除き、実施例1のような方法で実施例2〜12のペプチドを製造した。
損傷した軟骨組織移植片(explant)を使用した軟骨再生効果確認
軟骨組織移植片(articular chondrocyte explant)は、地域の屠殺場(大韓民国大田市梧井洞所在)で屠殺されて1時間が経過していない3才以下の牛のかかとの関節から分離して使用した。関節から骨を除いた軟骨の部分を均一に切り出した後、手術用ナイフで約3mmx3mmに切って軟骨組織移植片を作った。先端を短く切って研磨した21ゲージ(21G)の注射針を使用して移植片の中央に表面と垂直となるように均一に穴をあけて損傷部位を作った。
関節軟骨ペレット(pellet)を使用した軟骨再生効果確認
<遺伝子発現に対する実施例1のペプチドの影響>
関節軟骨細胞(articular chondrocyte)の性質を生体組織と類似するように維持するために細胞をペレット形態に作って培養した。
forward primer:5’−CAGGACCAAAGGGACAGAAA−3’(配列番号13)
reverse primer:5’−GGTTGCCTTGAAATCCTTGA−3’(配列番号14)
MMP13 (product size:600bp)
forward primer:5’−ATGGACCCTCTGGTCTGTTG−3’(配列番号15)
reverse primer:5’−CGTGTTTTGGAAATCCCAGT−3’(配列番号16)
Type X collagen (product size:454bp)
forward primer:5’−CAGTCAAGGGCCTTAATGGA−3’(配列番号17)
reverse primer:5’−CCTGAAGCCTGATCCAGGTA−3’(配列番号18)
GAPDH(Glyceraldehyde−3−phosphate dehydrogenase) (product size:345bp)
forward primer:5’−ACCCAGAAGACTGTGGATGG−3’(配列番号19)
reverse primer:5’−CCCAGCATCGAAGGTAGAAG−3’(配列番号20)
具体的に、次のような条件でPCRを行った。PCR反応額はcDNA 1ul、2x Taq polymerase master mix(Solgent)10ul、各primer(10pmole/ul)0.5ulずつ、蒸溜水8ulを使用した。PCR反応は、摂氏94度で2分間変成させた後、摂氏94度で30秒、摂氏58度で45秒、摂氏72度で1分の条件で、Type II collagen、Type X collagen、MMP13は、各々32サイクル、GAPDHは26サイクルのあいだ増幅させた。PCR増幅産物は、1% agarose gelで電気泳動し、EtBr(ethidium bromide、2ug/ml)で15分間染色した後、UV上で確認し、Image J(NIH)プログラムを使用してGAPDH発現量で平均化させた後、相対的な発現量を比較した。
また、実施例1のペプチドの代わりに実施例2〜12のペプチド各々を使用したものを除き、<遺伝子発現に対する実施例1のペプチドの影響>と同一の方法でペプチドの影響を評価した。実施例1〜12のペプチドが軟骨組織培養細胞のうちコラーゲンタイプIIの発現に及ぼす影響に対する実験結果を下記表2に示した。
変形性関節症モデルを利用した軟骨再生効果確認
すべての動物実験はSamsung Biomedical Research Institute(SBRI、Seoul、Korea)のInstitutional Animal Care and Use Committeeの承認の下に、the Institute of Laboratory Animal Resources(ILAR)guidelineを遵守して18〜22週齢の体重3〜3.5kgの雄ウサギ(New Zealand whites rabbits;(株)オリエントバイオ(韓国))10匹に対する実験を実施した。関節軟骨変成は膝前十字靭帯を手術で切開した後、4週間ケージで飼育して誘発させ、対照群と試験群で分けて実験を行った。
Claims (7)
- 下記一般式(I)で示されるペプチド、または薬学的に許容可能なその塩、
X1−Leu−X2−Leu−X3 (I)
前記式で、X1はGluまたはAspであり、X2はHis、LysまたはArgであり、X3はAspまたはGluであり、前記Gluはグルタミン酸、Aspはアスパラギン酸、Leuはロイシン、Hisはヒスチジン、LysはリシンでArgはアルギニンである。 - 前記X1はGluで、前記X2はHisであり、前記X3はAspであることを特徴とする請求項1に記載のペプチド、または薬学的に許容可能なその塩。
- 請求項1または請求項2のペプチド、または薬学的に許容可能なその塩を有効成分として含んでいることを特徴とする組成物であって、軟骨損傷または関節炎のうちから選択された一つ以上の、治療または予防用組成物。
- 前記治療または予防は軟骨組織再生、軟骨組織基質分解酵素発現抑制、および軟骨組織骨化抑制のうちから選択された一つ以上によるものであることを特徴とする請求項3に記載の組成物。
- 前記関節炎は、軟骨および軟骨下骨の変成を伴う関節疾患であることを特徴とする請求項3に記載の組成物。
- 前記組成物は、薬学組成物であることを特徴とする請求項3に記載の組成物。
- 請求項1または請求項2のペプチド、または薬学的に許容可能なその塩およびTGFβ1(Transforming growth factor beta 1;形質転換成長因子ベータ1)を含むことを特徴とする組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020100062467A KR101029705B1 (ko) | 2010-06-30 | 2010-06-30 | 신규 펩타이드 및 그 용도 |
KR10-2010-0062467 | 2010-06-30 | ||
PCT/KR2011/004541 WO2012002668A2 (en) | 2010-06-30 | 2011-06-22 | Novel peptide and use thereof |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013513657A JP2013513657A (ja) | 2013-04-22 |
JP2013513657A5 JP2013513657A5 (ja) | 2014-02-27 |
JP5607176B2 true JP5607176B2 (ja) | 2014-10-15 |
Family
ID=44050220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012544408A Active JP5607176B2 (ja) | 2010-06-30 | 2011-06-22 | 新規ペプチドおよびその用途 |
Country Status (14)
Country | Link |
---|---|
US (1) | US8772241B2 (ja) |
EP (1) | EP2588491B1 (ja) |
JP (1) | JP5607176B2 (ja) |
KR (1) | KR101029705B1 (ja) |
CN (1) | CN102892776B (ja) |
AU (1) | AU2011272137B2 (ja) |
BR (1) | BR112012031587B1 (ja) |
CA (1) | CA2801010C (ja) |
ES (1) | ES2606778T3 (ja) |
MX (1) | MX2012015000A (ja) |
PL (1) | PL2588491T3 (ja) |
RU (1) | RU2525913C1 (ja) |
SG (1) | SG186120A1 (ja) |
WO (1) | WO2012002668A2 (ja) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104886564B (zh) * | 2015-05-12 | 2017-05-17 | 浙江海洋学院 | 一种路氏双髻鲨软骨血管生成抑制因子的用途 |
KR101644982B1 (ko) * | 2015-07-23 | 2016-08-02 | 주식회사 엔솔바이오사이언스 | 신규 펩타이드 및 그 용도 |
WO2017155234A1 (ko) * | 2016-03-09 | 2017-09-14 | 주식회사 바이오펩 | 염증성 질환의 예방 또는 치료용 펩타이드 및 이의 용도 |
US10913772B2 (en) | 2016-03-09 | 2021-02-09 | Kine Sciences Co., Ltd. | Peptide for preventing or treating inflammatory diseases and use thereof |
EP3428178A4 (en) | 2016-03-09 | 2019-09-04 | Bio Pep Co., Ltd. | PEPTIDE FOR THE PREVENTION OR TREATMENT OF INFLAMMATORY DISEASES AND USE THEREOF |
US10913771B2 (en) | 2016-03-09 | 2021-02-09 | Kine Sciences Co., Ltd. | Peptide for preventing or treating inflammatory diseases and use thereof |
KR101897122B1 (ko) | 2016-03-09 | 2018-09-10 | 주식회사 바이오펩 | 염증성 질환의 예방 또는 치료용 펩타이드 및 이의 용도 |
EP3489253B1 (en) * | 2016-07-20 | 2023-03-01 | Ensol Biosciences Inc. | Novel peptide and use thereof |
CN107670021B (zh) * | 2016-08-02 | 2020-09-18 | 富比积生物科技股份有限公司 | 五胜肽kttks在治疗退化性关节炎中的用途 |
WO2019054809A2 (ko) * | 2017-09-15 | 2019-03-21 | 주식회사 바이오펩 | 자가면역질환 및 골질환 치료제로서의 펩타이드의 용도 |
AU2018333776B2 (en) | 2017-09-15 | 2022-07-07 | Kine Sciences Co., Ltd. | Use of peptides as therapeutic agent for autoimmune diseases and bone diseases |
KR101995768B1 (ko) * | 2019-03-13 | 2019-07-03 | (주)엔솔바이오사이언스 | 신규 펩타이드 및 그 용도 |
KR20230167231A (ko) | 2022-05-31 | 2023-12-08 | 주식회사 엔솔바이오사이언스 | 염형태 변형 펩타이드의 제조방법 및 그를 이용하여 제조된 펩타이드 |
KR20230167253A (ko) | 2022-05-31 | 2023-12-08 | 주식회사 엔솔바이오사이언스 | 펩타이드 함유 액상제제 및 그 제조방법 |
KR20240086939A (ko) * | 2022-12-09 | 2024-06-19 | (주)케어젠 | 연골 재생용 펩타이드 및 이의 용도 |
KR20240086946A (ko) * | 2022-12-09 | 2024-06-19 | (주)케어젠 | 연골 재생용 펩타이드 및 이의 용도 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
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US5955343A (en) | 1992-12-28 | 1999-09-21 | Massachusetts Institute Of Technology | Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor |
US6638912B2 (en) * | 1995-05-01 | 2003-10-28 | The Regents Of The University Of California | Peptide compositions mimicking TGF-β activity |
US6727224B1 (en) * | 1999-02-01 | 2004-04-27 | Genetics Institute, Llc. | Methods and compositions for healing and repair of articular cartilage |
WO2006089023A2 (en) * | 2005-02-16 | 2006-08-24 | The Regents Of The University Of California | Pharmaceutical compositions for treating or preventing bone conditions |
US7687462B2 (en) | 1999-10-05 | 2010-03-30 | The Regents Of The University Of California | Composition for promoting cartilage formation or repair comprising a nell gene product and method of treating cartilage-related conditions using such composition |
US6716811B1 (en) * | 2000-07-20 | 2004-04-06 | Affymax, Inc. | Compounds having affinity for the granulocyte-colony stimulating factor receptor (G-CSFR) and associated uses |
WO2002062961A2 (en) | 2001-02-06 | 2002-08-15 | Massachusetts Institute Of Technology | Peptide scaffold encapsulation of tissue cells and uses thereof |
ES2304069B1 (es) * | 2003-08-22 | 2009-08-12 | Proyecto De Biomedicina Cima, S.L. | Peptidos con capacidad de unirse al factor transformante de crecimiento beta 1 (tgf-b1). |
US8039258B2 (en) * | 2004-09-28 | 2011-10-18 | Ethicon, Inc. | Tissue-engineering scaffolds containing self-assembled-peptide hydrogels |
US7888462B2 (en) * | 2007-01-22 | 2011-02-15 | Acologix, Inc. | Peptide composition and a method of promoting cartilage formation |
CA2618163A1 (en) * | 2008-02-07 | 2009-08-07 | K. W. Michael Siu | Head and neck cancer biomarkers |
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2010
- 2010-06-30 KR KR1020100062467A patent/KR101029705B1/ko active Protection Beyond IP Right Term
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2011
- 2011-06-22 AU AU2011272137A patent/AU2011272137B2/en active Active
- 2011-06-22 ES ES11801075.0T patent/ES2606778T3/es active Active
- 2011-06-22 SG SG2012088381A patent/SG186120A1/en unknown
- 2011-06-22 BR BR112012031587-0A patent/BR112012031587B1/pt active IP Right Grant
- 2011-06-22 CA CA2801010A patent/CA2801010C/en active Active
- 2011-06-22 JP JP2012544408A patent/JP5607176B2/ja active Active
- 2011-06-22 RU RU2013101051/04A patent/RU2525913C1/ru active
- 2011-06-22 PL PL11801075T patent/PL2588491T3/pl unknown
- 2011-06-22 WO PCT/KR2011/004541 patent/WO2012002668A2/en active Application Filing
- 2011-06-22 CN CN201180004884.2A patent/CN102892776B/zh active Active
- 2011-06-22 EP EP11801075.0A patent/EP2588491B1/en active Active
- 2011-06-22 MX MX2012015000A patent/MX2012015000A/es active IP Right Grant
- 2011-06-22 US US13/701,465 patent/US8772241B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
BR112012031587B1 (pt) | 2021-07-13 |
CA2801010A1 (en) | 2012-01-05 |
CN102892776B (zh) | 2014-07-16 |
KR101029705B1 (ko) | 2011-04-18 |
WO2012002668A3 (en) | 2012-04-26 |
AU2011272137B2 (en) | 2016-09-29 |
SG186120A1 (en) | 2013-01-30 |
CN102892776A (zh) | 2013-01-23 |
EP2588491A4 (en) | 2013-12-04 |
EP2588491B1 (en) | 2016-09-14 |
RU2525913C1 (ru) | 2014-08-20 |
US8772241B2 (en) | 2014-07-08 |
AU2011272137A1 (en) | 2013-02-14 |
CA2801010C (en) | 2015-10-13 |
BR112012031587A2 (pt) | 2017-12-05 |
PL2588491T3 (pl) | 2017-03-31 |
ES2606778T3 (es) | 2017-03-27 |
WO2012002668A2 (en) | 2012-01-05 |
US20130109626A1 (en) | 2013-05-02 |
RU2013101051A (ru) | 2014-08-10 |
MX2012015000A (es) | 2013-02-07 |
EP2588491A2 (en) | 2013-05-08 |
JP2013513657A (ja) | 2013-04-22 |
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