KR20050012717A - 수식 펩티드의 제조 방법 - Google Patents
수식 펩티드의 제조 방법Info
- Publication number
- KR20050012717A KR20050012717A KR10-2004-7010361A KR20047010361A KR20050012717A KR 20050012717 A KR20050012717 A KR 20050012717A KR 20047010361 A KR20047010361 A KR 20047010361A KR 20050012717 A KR20050012717 A KR 20050012717A
- Authority
- KR
- South Korea
- Prior art keywords
- group
- amino acid
- peptide
- modified
- peptide fragment
- Prior art date
Links
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- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000004804 winding Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
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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
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
-
- 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
- C07K14/465—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from birds
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (23)
- 아미노산 또는/및 비아미노산으로 이루어지는 원하는 배열을 가지고, 그 중 적어도 하나의 아미노산 또는 비아미노산이 식 1; -A(R)-(식 중에서, A는 아미노산 또는 비아미노산을 나타내고, R은 A의 측쇄에 결합되어 있는 수식을 위해 도입된 치환기를 나타냄)로 나타내어지는 수식(修飾)을 받은 아미노산 또는 비아미노산이며, 또한, 아미노산 또는 비아미노산의 측쇄에서의 수산기(水酸基), 아미노기, 구아니디노기, 이미다졸릴기, 인돌릴기, 메르캅토기 및 카르복시기로 이루어지는 군에서 선택되는 1종 이상의, 펩티드 단편(斷片) 제작에 있어서 바람직하지 않은 부반응을 야기할 가능성을 가진 반응성 작용기가 보호기에 의해 보호되어 있는 펩티드 단편을 약산성 이탈(離脫) 수지 상에서 제작하고, 이어서, 약산성 조건에서 상기 펩티드 단편에서의 보호기를 탈리시키지 않고 상기 펩티드 단편을 약산성 이탈 수지로부터 이탈시키는 것을 특징으로 하는, 수식을 받은 아미노산 또는 비아미노산을 하나 이상 포함하는 보호되어 있는 펩티드 단편의 제조 방법.
- 제1항에 있어서,(a) 아미노산 또는/및 비아미노산으로 이루어지는 원하는 배열을 가지고, 또한 아미노산 또는 비아미노산의 측쇄에서의 수산기, 아미노기, 구아니디노기, 이미다졸릴기, 인돌릴기, 메르캅토기 및 카르복시기로 이루어지는 군에서 선택되는 1종 이상의, 펩티드 단편 제작에 있어서 바람직하지 않은 부반응을 야기할 가능성을 가진 반응성 작용기가 보호기에 의해 보호되어 있는 펩티드 단편을 약산성 이탈 수지 상에서 제작하고,(b) 상기 펩티드 단편을 약산성 이탈 수지 상에서 이탈시키지 않고, 치환기 R에 의해 수식을 받는 아미노산 또는 비아미노산 A의 측쇄에서의 반응성 작용기에 보호기가 도입되어 있는 경우에는 상기 보호기를 탈보호하고,(c) 상기 탈보호된 측쇄를 치환기 R로 수식하고,(d) 약산성 조건에서 상기 펩티드 단편에서의 보호기를 탈리시키지 않고 상기 펩티드 단편을 약산성 이탈 수지로부터 이탈시키는것을 특징으로 하는 펩티드 단편의 제조 방법.
- 제2항에 있어서,치환기 R에 의해 수식을 받는 상기 아미노산 또는 비아미노산 A의 측쇄에서의 반응성 작용기의 보호기가 실릴계 보호기이며, 상기 보호기의 탈보호에 플루오르화 4급 암모늄을 이용하는 것을 특징으로 하는 펩티드 단편의 제조 방법.
- 제3항에 있어서,상기 실릴계 보호기가, t-부틸디메틸실릴(TBDMS), t-부틸디페닐실릴(TBDPS), 트리이소프로필실릴(TIPS), 트리이소부틸실릴(TIBS), t-헥실디메틸실릴(ThxDMS) 또는 트리페닐실릴(TPS)이며, 플루오르화 4급 암모늄이 테트라부틸암모늄플루오라이드 (TBAF), 테트라에틸암모늄플루오라이드(TEF) 또는 암모늄플루오라이드인 것을특징으로 하는 펩티드 단편의 제조 방법.
- 제1항 내지 제4항 중 어느 한 항에 있어서,상기 A가 세린, 트레오닌, 시스테인, 호모시스테인, 리진, 오르니틴, 글루탐산, 2-아미노아디프산, 디아미노아세트산, 2-아미노말론산, 아스파라긴산, 티로신 또는 아스파라긴이며, 상기 R이 에스테르 결합, 에테르 결합, 티오에테르 결합, 디설파이드 결합, 아미드 결합, O-글루코사이드 결합 또는 N-글루코사이드 결합을 통하여 상기 A의 측쇄의 반응성 치환기에 결합되어 있는 것을 특징으로 하는 펩티드 단편의 제조 방법.
- 제5항에 있어서,상기 A가 세린 또는 트레오닌이며, 상기 R이 에스테르 결합을 통하여 상기 A의 측쇄의 수산기에 결합되어 있는 것을 특징으로 하는 펩티드 단편의 제조 방법.
- 제6항에 있어서,상기 펩티드 단편이, 그렐린(Ghrelin) 또는 그 유도체, 또는 상기 그렐린 또는 그 유도체의 중의 수식을 받은 아미노산을 포함하는 펩티드 단편인 것을 특징으로 하는 펩티드 단편의 제조 방법.
- (a) 제1항 내지 제7항 중 어느 한 항의 방법에 의해서 수식을 받은 아미노산또는 비아미노산을 하나 이상 포함하는 보호되어 있는 펩티드 단편을 제조하고, 상기 (a)의 펩티드 단편과는 별개로, (b) 수식을 받은 아미노산 또는 비아미노산을 포함하지 않고, 또한, 아미노산 또는 비아미노산의 측쇄에서의 수산기, 아미노기, 구아니디노기, 이미다졸릴기, 인돌릴기, 메르캅토기 및 카르복시기로 이루어지는 군에서 선택되는 1종 이상의, 바람직하지 않은 부반응을 야기할 가능성을 가진 반응성 작용기가 보호되어 있는 펩티드 단편을 제조하고, 상기 (a) 및 (b)로 제조된 펩티드 단편을 축합하는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제8항에 있어서,상기 펩티드 단편의 축합이, 축합제를 이용하여 행해지는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제9항에 있어서,상기 축합제가, 2-(1-하이드로벤조트리아졸-1-일)-1,1,3,3-테트라메틸우로늄헥사플루오로포스페이트(HBTU), 2-(1-하이드로벤조트리아졸-1-일)-1,1,3,3-테트라메틸우로늄테트라플루오로보레이트(TBTU), 디페닐포스포릴아지드(DPPA), 디페닐포스포로시아니데이트(DEPC), 디이소프로필카르보디이미드(DIPC), 디사이클로헥실카르보디이미드(DCC) 또는 1-에틸-3-(3-디메틸아미노프로필)카르보디이미드(EDC)인 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제9항에 있어서,상기 축합제가, 디이소프로필카르보디이미드(DIPC), 디사이클로헥실카르보디이미드(DCC) 또는 1-에틸-3-(3-디메틸아미노프로필)카르보디이미드(EDC)이며, 상기 축합제를 이용하는 펩티드 단편 (a)와 (b)의 축합이, 1-하이드록시벤조트리아졸 (H0Bt), 1-하이드록시숙신이미드(H0Su) 또는 3,4-디하이드로-3-하이드록시-4-옥소-벤조트리아진(H00Bt)의 존재 하에서 행해지는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제8항 내지 제11항 중 어느 한 항에 있어서,수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편을, 효소법 또는/및 유전자 재조합법에 의해 제조하는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제12항에 있어서,수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편을,공정 (1); 상기 펩티드 단편의 아미노산 배열을 가지는 펩티드(이하, 본 항에 있어서 목적 펩티드라 함)를 코딩하는 염기 배열, 또는 상기 목적 펩티드에, 원하는 바에 따라 링커 배열(linker sequence)을 통하여 보호 펩티드가 부가되어 있는 융합 단백질을 코딩하는 염기 배열 중 어느 하나를 가지는 발현 벡터에 의해 형질전환된 세포를 배양하고, 상기 배양물로부터 상기 목적 펩티드 또는 상기 융합 단백질을 채취하는 공정;공정 (2); 공정 (1)에서 상기 융합 단백질을 채취한 경우, 얻어진 상기 융합 단백질로부터, 보호 펩티드 및 원하는 바에 따라 상기 링커 배열과 상기 목적 펩티드를 절단 분리하고, 원하는 바에 따라 상기 목적 펩티드를 추가로 정제하는 공정; 및공정 (3); 공정 (1) 또는 (2)에서 얻어진 상기 목적 펩티드의 측쇄에서의 수산기, 아미노기, 구아니디노기, 이미다졸릴기, 인돌릴기, 메르캅토기 및 카르복시기로 이루어지는 군에서 선택되는 1종 이상의, 바람직하지 않은 부반응을 야기할 가능성을 가진 반응성 작용기를 보호기에 의해 보호하는 공정;을 포함하는 방법에 의해 제조하는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제13항에 있어서,공정 (2)에서의 상기 보호 펩티드 및 원하는 바에 따라 상기 링커 배열과 상기 목적 펩티드의 절단 분리가, OmpT 프로테아제 또는 그의 유도체 및 Kex2 프로테아제 또는 그의 유도체를 이용하여 2단계로 행해지는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제13항 또는 제14항에 있어서,상기 링커 배열이, 배열 번호 27에 기재된 배열인 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제12항 내지 제15항 중 어느 한 항에 있어서,상기 펩티드 단편이, 그렐린 또는 그의 유도체 중의 수식을 받은 아미노산 또는 비아미노기를 포함하지 않는 펩티드 단편인 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제12항 내지 제16항 중 어느 한 항에 있어서,수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 상기 펩티드 단편을, pH 4∼8의 용액 중에서 정제 및 보존하는 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 제12항 내지 제17항 중 어느 한 항에 있어서,상기 보호기가 Boc기인 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
- 공정 (1); 원하는 아미노산 배열을 가지는 펩티드(이하, 본 항에 있어서 목적 펩티드라고 함)를 코딩하는 염기 배열 또는 상기 목적 펩티드에, 원하는 바에따라 링커 배열을 통하여 보호 펩티드가 부가되어 있는 융합 단백질을 코딩하는 염기 배열 중 어느 하나를 가지는 발현 벡터에 의해 형질전환된 세포를 배양하여, 상기 배양물로부터 상기 목적 펩티드 또는 상기 융합 단백질을 채취하는 공정;공정 (2); 공정 (1)에서 상기 융합 단백질을 채취한 경우, 얻어진 상기 융합 단백질로부터, 보호 펩티드 및 원하는 바에 따라 상기 링커 배열과 상기 목적 펩티드를 절단 분리하고, 원하는 바에 따라 추가로 정제하는 공정;공정 (3); 공정 (1) 또는 (2)에서 얻어진 상기 목적 펩티드의 측쇄에서의 수산기, 아미노기, 구아니디노기, 이미다졸릴기, 인돌릴기, 메르캅토기 및 카르복시기로 이루어지는 군에서 선택되는 1종 이상의, 바람직하지 않은 부반응을 야기할 가능성을 가진 반응성 치환기를 보호기에 의해 보호하는 공정; 및공정 (4); 공정 (3)에서 얻어진 보호되어 있는 상기 목적 펩티드를 pH 4∼8의 용액 중에서 정제 및 보존하는 공정을 포함하는 방법에 의해 제조하는 것을 특징으로 하는, 수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편의 제조 방법.
- 제19항에 있어서,상기 보호기가 Boc기인 것을 특징으로 하는, 수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편의 제조 방법.
- 제19항 또는 제20항에 있어서,공정 (2)에서의 상기 보호 펩티드 및 원하는 바에 따라 상기 링커 배열과 상기 목적 펩티드의 절단 분리가, OmpT 프로테아제 또는 그의 유도체 및 Kex2 프로테아제 또는 그의 유도체를 이용하여 2단계로 행해지는 것을 특징으로 하는, 수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편의 제조 방법.
- 제19항 내지 제21항 중 어느 한 항에 있어서,상기 링커 배열이, 배열 번호 27에 기재된 배열인 것을 특징으로 하는, 수식을 받은 아미노산 또는 비아미노산을 포함하지 않는 보호되어 있는 펩티드 단편의 제조 방법.
- 제19항 내지 제22항 중 어느 한 항에 있어서,상기 펩티드 단편이, 그렐린 또는 그의 유도체 중의 수식을 받은 아미노산 또는 비아미노기를 포함하지 않는 펩티드 단편인 것을 특징으로 하는 수식 펩티드 또는 단백질의 제조 방법.
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JP2002109761 | 2002-04-11 | ||
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PCT/JP2003/004590 WO2003084983A1 (fr) | 2002-04-11 | 2003-04-10 | Procede de production d'un peptide modifie |
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KR (1) | KR101036524B1 (ko) |
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US7357947B2 (en) * | 2001-09-10 | 2008-04-15 | Biomet, Inc. | Bone graft material incorporating demineralized bone matrix and lipids |
KR20050012224A (ko) * | 2002-05-21 | 2005-01-31 | 다이이찌 산토리 파마 가부시키가이샤 | 그렐린 함유 의약 조성물 |
BR0314619A (pt) * | 2002-09-18 | 2005-08-02 | Univ Montreal Ct Hospitalier Chum | Análogos de ghrh |
CN102225966B (zh) | 2004-10-19 | 2012-12-26 | 隆萨股份公司 | 用于固相肽合成的方法 |
US20070042501A1 (en) * | 2005-08-20 | 2007-02-22 | Institute Of Nuclear Energy Research | A novel technology for the purity assay of TRODAT-1 raw material |
US7763707B2 (en) * | 2006-03-13 | 2010-07-27 | Liat Mintz | Use of ghrelin splice variant for treating cachexia and/or anorexia and/or anorexia-cachexia and/or malnutrition and/or lipodystrophy and/or muscle wasting and/or appetite-stimulation |
CN104853778A (zh) | 2012-10-24 | 2015-08-19 | 第一三共株式会社 | 用于肌萎缩性侧索硬化的治疗剂 |
SG11201506885UA (en) | 2013-03-21 | 2015-09-29 | Sanofi Aventis Deutschland | Synthesis of cyclic imide containing peptide products |
EP2976331B1 (en) | 2013-03-21 | 2017-03-01 | Sanofi-Aventis Deutschland GmbH | Synthesis of hydantoin containing peptide products |
CN106459149A (zh) * | 2014-03-04 | 2017-02-22 | 莫图斯治疗公司 | H‑inp‑(d)bal‑(d)trp‑phe‑apc‑nh2及其可药用盐的液相合成的方法 |
EP3284851B1 (en) * | 2015-04-14 | 2020-12-23 | Hitgen Inc. | Method for solid-phase synthesis of dna-encoded chemical library |
EP3986919A1 (en) * | 2019-06-18 | 2022-04-27 | Fresenius Kabi iPSUM S.r.l. | Process for the manufacture of glucagon |
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CA2198966C (en) | 1996-03-04 | 2011-06-21 | Yuji Suzuki | Method for cleaving chimeric protein using processing enzyme |
CA2198968C (en) | 1996-03-04 | 2010-02-09 | Toyofumi Masuda | Process for production of secretory kex2 derivatives |
AU765206B2 (en) | 1998-01-30 | 2003-09-11 | Daiichi Sankyo Company, Limited | Process for producing peptide with the use of accessory peptide |
US7344856B1 (en) | 1999-03-04 | 2008-03-18 | Asubio Pharma Co. Ltd. | Method of controlling cleavage by OmpT protease |
ES2154590B1 (es) | 1999-05-20 | 2001-11-01 | Lipotec Sa | Procedimiento de sintesis de peptidos en fase solida |
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AU2003236080B8 (en) | 2009-07-02 |
EP1493747A1 (en) | 2005-01-05 |
BRPI0306644B8 (pt) | 2021-05-25 |
CN100491395C (zh) | 2009-05-27 |
CA2472235A1 (en) | 2003-10-16 |
US7138489B2 (en) | 2006-11-21 |
ES2400703T3 (es) | 2013-04-11 |
US20050131208A1 (en) | 2005-06-16 |
IL162780A0 (en) | 2005-11-20 |
AU2003236080A1 (en) | 2003-10-20 |
WO2003084983A1 (fr) | 2003-10-16 |
KR101036524B1 (ko) | 2011-05-24 |
CA2472235C (en) | 2012-05-22 |
EP1493747B1 (en) | 2012-12-19 |
AU2003236080B2 (en) | 2009-06-11 |
EP1493747A4 (en) | 2007-11-28 |
CN1612891A (zh) | 2005-05-04 |
BRPI0306644B1 (pt) | 2018-02-14 |
IL162780A (en) | 2013-10-31 |
BR0306644A (pt) | 2005-04-26 |
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