JP6190825B2 - 二官能性ペプチド - Google Patents
二官能性ペプチド Download PDFInfo
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- JP6190825B2 JP6190825B2 JP2014555282A JP2014555282A JP6190825B2 JP 6190825 B2 JP6190825 B2 JP 6190825B2 JP 2014555282 A JP2014555282 A JP 2014555282A JP 2014555282 A JP2014555282 A JP 2014555282A JP 6190825 B2 JP6190825 B2 JP 6190825B2
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- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
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- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
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- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
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Images
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/8146—Metalloprotease (E.C. 3.4.24) inhibitors, e.g. tissue inhibitor of metallo proteinase, TIMP
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
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- 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
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C07K2319/00—Fusion polypeptide
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- C07K2319/50—Fusion polypeptide containing protease site
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- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
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Description
− 皮膚の厚みを低減させる目的での皮膚の攻撃的な処置に相当する、落屑または皮膚擦傷、
− それぞれ、皺を埋める効果、および一時的に皺を緩和させる、標的の筋肉の麻痺を示す、ヒアルロン酸またはボツリヌストキシンの皺取り注入。しかしながら、これらの技術は高価で、短期的な効果しか示さない、
− 保湿製品、皺防止クリームまたはスムージングクリームなどの表皮トリートメントの使用。これらの製品は皺の出現を遅らせるもののすでに形成された皺の修正はしない、
− 自家幹細胞に基づく療法。これはまだほとんど究められていない。
− R1は、H、または2〜22個の炭素を含むアルコキシル鎖に相当し、
− (AA)nは、AAが任意のアミノ酸またはアミノ酸誘導体から成り、および/またはnが0〜3である、ペプチド鎖に相当し、
− R2は、H、または1〜24個の炭素を含むアルキル鎖に相当している。
− 少なくとも三回反復されたヘキサペプチドに相当し、コラーゲン合成を刺激するためエラスチンを結合させる受容体タンパク質に結合できる、第一のペプチド部分A、
− ウロキナーゼプロテアーゼの競合阻害物質として作用し、かつ前記プロテアーゼにより開裂され得るテトラペプチドに相当する、第二のペプチド部分B、
− 前記プロテイナーゼの阻害を可能にするためマトリックスメタロプロテイナーゼの少なくとも一つの活性部位を占有するトリペプチドに相当する、第三のペプチド部分C;
という三つのペプチド部分A、BおよびCを含む配列を呈する、二官能性ペプチドに関する。
− X1は、任意のアミノ酸に相当し、
− X2は、Val、Thr、Gln、Ala、Leuの中から選択されるアミノ酸に相当し、
− X3は、Ala、Leu、Ileの中から選択されるアミノ酸に相当している。
− Z1は、Gly、Ile、Leuの中から選択されるアミノ酸に相当し、
− Z2は、Leu、Phe、Ala、Ile、Valの中から選択されるアミノ酸に相当している。
S1:N−(Val−Gly−Val−Ala−Pro−Gly)n−Arg−Val−Arg−Leu−Gly−Ile−Leu−OH
という配列番号1に相当する配列S1を呈し、
ここで、NおよびOHは、それぞれ前記ペプチドの末端のN末端およびC末端に相当し、n=3である。
− 有利にもコラーゲン合成を増大させる能力を示す、部分Aと呼ばれる第一のペプチド部分、
− 好ましくは、一つのプロテアーゼ、すなわちウロキナーゼにより認識される配列を呈し、このときこのプロテアーゼによって開裂され得る、部分Bと呼ばれる第二のペプチド部分、
− MMPを阻害することのできる、部分Cと呼ばれる第三のペプチド部分。
S1:N−(Val−Gly−Val−Ala−Pro−Gly)n−Arg−Val−Arg−Leu−Gly−Ile−Leu−OH
という配列を呈する。
35〜75才の健康な患者に対して行なわれた外科手術中に得た腹部の皮膚の生検試料から、真皮線維芽細胞を単離する。
− ペプチド1(pept1):配列S1を呈するペプチド、
− ペプチド2(pept2):配列N−(Val−Gly−Val−Ala−Pro−Gly)3−Arg−Val−Arg−Leu−OH
− ペプチド3(pept3):N−(Val−Gly−Val−Ala−Pro−Gly)3−OH
− ペプチド4(pept4):N−Arg−Val−Arg−Leu−Gly−Ile−Leu−OH
− ペプチド5(pept5):N−Gly−Ile−Leu−OH
100μg/mlの濃度の複数の異なるペプチド(pept1〜pept5)の存在下で、線維芽細胞の培養におけるI型およびIII型コラーゲンの遺伝子発現も同様に試験した。
多少、年を取った患者(35、42および53才)に由来する真皮線維芽細胞を培養し、配列S1を呈する本発明に係る二官能性ペプチドを、I型およびIII型コラーゲンのタンパク質発現および遺伝子発現について試験した。二つのタイプのコラーゲンのタンパク質発現に関して得た結果は、図5に見られる。コラーゲン合成に対する本発明に係るペプチドの作用は、線維芽細胞がより高齢の患者に由来するものである場合により大きいことが分かる。
プロテイナーゼMMP−1の活性化カスケードの上流側の酵素であるウロキナーゼに対する本発明に係る二官能性ペプチドの作用を評価した。
次に、ウロキナーゼにより活性化されるカスケードの下流側の酵素であるMMP−1の活性に対する、本発明に係る二官能性ペプチドの効果を直接評価した。
細胞周囲レベルでは、およそ10−4Mの過剰のウロキナーゼが観察される。したがって、ウロキナーゼは本発明に係るペプチドの部分Bのアルギニン(Arg)残基レベルで特に作用するので、ペプチドを開裂することができる。
発明者らは、I型コラゲナーゼ、MMP−1のポケットP’1、P’2およびP’3を占有する能力を理由として配列Gly−Ile−Leuを選択した。MMP−1の活性を、10−5、10−4および10−3Mの濃度の配列Gly−Ile−Leuを呈するペプチド5の存在下または不在下で、その合成基質DNP−Pro−Cha−Gly−Cys(Me)−His−Ala−Lys(N−Me−Abz)−NH2上で試験した。
Claims (13)
- コラーゲン合成を活性化しマトリックスメタロプロテイナーゼの産生を阻害することのできる二官能性ペプチドにおいて、
− 少なくとも三回反復されたヘキサペプチドに相当し、コラーゲン合成を刺激するためエラスチンを結合させる受容体タンパク質に結合できる、第一のペプチド部分Aであって、コラーゲン合成を刺激する第一のペプチド部分Aが配列X1−Gly−X2−X3−Pro−Glyを呈し、この配列が少なくとも三回反復され、ここで、 X1は、任意のアミノ酸に相当し、 X2は、Val、Thr、Gln、Ala、Leuの中から選択されるアミノ酸に相当し、X3は、Ala、Leu、Ileの中から選択されるアミノ酸に相当している、
− ウロキナーゼプロテアーゼの競合阻害物質として作用し、かつ前記プロテアーゼにより開裂され得るテトラペプチドに相当する、第二のペプチド部分Bであって、 プロテアーゼにより開裂可能な第二のペプチド部分Bが、配列Arg−Y1−Arg−Y2を呈し、ここでY1とY2はSer、Tyr、Gly、Ala、Arg、Val、Leuの中から選択されるアミノ酸に各々相当している、
− 前記プロテイナーゼの阻害を可能にするためマトリックスメタロプロテイナーゼの少なくとも一つの活性部位を占有するトリペプチドに相当する、第三のペプチド部分Cであって、マトリックスメタロプロテイナーゼの阻害を可能にする第三のペプチド部分Cが、配列Z1−Ile−Z2を呈し、ここで、 Z1は、Gly、Ile、Leuの中から選択されるアミノ酸に相当し、 Z2は、Leu、Phe、Ala、Ile、Valの中から選択されるアミノ酸に相当している、
という三つのペプチド部分A、BおよびCを含む配列を呈することを特徴とする、二官能性ペプチド。 - 前記ペプチドの第一のペプチド部分Aが、配列Val−Gly−Val−Ala−Pro−Glyを呈することを特徴とする、請求項1に記載の二官能性ペプチド。
- 前記ペプチドの第二のペプチド部分Bが、配列Arg−Val−Arg−Leuを呈することを特徴とする、請求項1に記載の二官能性ペプチド。
- 前記ペプチドの第三のペプチド部分Cが、配列Gly−Ile−Leuを呈することを特徴とする、請求項1に記載の二官能性ペプチド。
- 配列番号1に相当する、
S1:N−(Val−Gly−Val−Ala−Pro−Gly)n−Arg−Val−Arg−Leu−Gly−Ile−Leu−OH
という配列S1を呈し、ここで、NおよびOHはそれぞれ前記ペプチドの末端のN末端およびC末端に相当し、n=3であることを特徴とする、請求項1〜4のいずれか一つに記載の二官能性ペプチド。 - 配列番号2〜配列番号26の配列の一つに相当することを特徴とする、請求項1〜4のいずれか一つに記載の二官能性ペプチド。
- 凍結乾燥された形で保存されることを特徴とする、請求項1〜6のいずれか一つに記載の二官能性ペプチド。
- 請求項1〜7のいずれか一つに記載の二官能性ペプチドを組込んだ、慢性瘢痕形成疾患の治療のための化粧品組成物および/または医薬組成物。
- 焼痂または潰瘍の治療のための請求項8に記載の化粧品組成物および/または医薬組成物。
- 請求項1〜7のいずれか一つに記載の二官能性ペプチドを組込んだ、真皮組織の修復および/または再生のための化粧品組成物および/または医薬組成物。
- 皮膚老化の治療のための請求項10に記載の化粧品組成物および/または医薬組成物。
- 請求項1〜7のいずれか一つに記載の二官能性ペプチドを組込んだ化粧品組成物および/または医薬組成物。
- 二官能性ペプチドの濃度が10μg/mL〜1mg/mLであり、好ましくは、ほぼ100μg/mLに等しい、請求項12に記載の化粧品組成物および/または医薬組成物。
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FR1250932A FR2986233B1 (fr) | 2012-02-01 | 2012-02-01 | Peptide bifonctionnel |
FR1250932 | 2012-02-01 | ||
PCT/FR2013/000033 WO2013114013A1 (fr) | 2012-02-01 | 2013-01-31 | Peptide bifonctionnel |
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JP2015506956A JP2015506956A (ja) | 2015-03-05 |
JP6190825B2 true JP6190825B2 (ja) | 2017-08-30 |
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CN111961119B (zh) * | 2020-09-02 | 2021-03-12 | 方晓东 | 多肽在制备促进胶原蛋白分泌的药物或化妆品中的用途 |
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AUPP472398A0 (en) * | 1998-07-17 | 1998-08-13 | University Of Sydney, The | Protease susceptibility II |
FR2826266B1 (fr) * | 2001-06-26 | 2005-02-25 | Oreal | Composition cosmetique ou dermatologique comprenant une association entre un compose de la famille des n-acylaminoamides et au moins un inhibiteur de metalloproteinases matricielles |
US7186693B2 (en) * | 2001-08-16 | 2007-03-06 | Kimberly - Clark Worldwide, Inc. | Metalloproteinase inhibitors for wound healing |
AU2003255621A1 (en) * | 2002-06-03 | 2003-12-19 | L'oreal | Topical use of at least one double-stranded rna oligonucleotide (ds rna) |
FR2854896B1 (fr) | 2003-05-16 | 2007-08-17 | Mayoly Spindler Lab | Nouveaux tensioactifs, compositions les comprenant |
DE102004055541A1 (de) | 2004-11-17 | 2006-05-18 | Henkel Kgaa | Kosmetische und dermatologische Zusammensetzungen zur Behandlung reifer Haut |
DE102004039550A1 (de) * | 2004-08-13 | 2006-02-23 | Henkel Kgaa | Kosmetische und dermatologische Zusammensetzungen mit (2-Hydroxyethyl)harnstoff |
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NZ628660A (en) | 2015-12-24 |
AU2013214039A1 (en) | 2014-09-04 |
RU2639573C2 (ru) | 2017-12-21 |
FR2986233B1 (fr) | 2014-02-28 |
PT2809342T (pt) | 2017-02-21 |
HK1203836A1 (en) | 2015-11-06 |
EP2809342A1 (fr) | 2014-12-10 |
WO2013114013A1 (fr) | 2013-08-08 |
US20150031633A1 (en) | 2015-01-29 |
DK2809342T3 (en) | 2017-02-20 |
ES2631030T3 (es) | 2017-08-25 |
US9115212B2 (en) | 2015-08-25 |
FR2986233A1 (fr) | 2013-08-02 |
KR20140134282A (ko) | 2014-11-21 |
HUE031782T2 (en) | 2017-08-28 |
CN104159599A (zh) | 2014-11-19 |
PL2809342T3 (pl) | 2017-06-30 |
CA2863472A1 (fr) | 2013-08-08 |
JP2015506956A (ja) | 2015-03-05 |
CN104159599B (zh) | 2017-02-01 |
KR101999283B1 (ko) | 2019-07-11 |
CA2863472C (fr) | 2017-06-06 |
AU2013214039B2 (en) | 2016-12-01 |
EP2809342B1 (fr) | 2016-12-21 |
RU2014134287A (ru) | 2016-03-20 |
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