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WO2005071071A1 - Proteine de fusion ptd-choline acetyltransferase humaine et son application - Google Patents

Proteine de fusion ptd-choline acetyltransferase humaine et son application Download PDF

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Publication number
WO2005071071A1
WO2005071071A1 PCT/CN2005/000086 CN2005000086W WO2005071071A1 WO 2005071071 A1 WO2005071071 A1 WO 2005071071A1 CN 2005000086 W CN2005000086 W CN 2005000086W WO 2005071071 A1 WO2005071071 A1 WO 2005071071A1
Authority
WO
WIPO (PCT)
Prior art keywords
fusion protein
chat
seq
disease
sequence
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.)
Ceased
Application number
PCT/CN2005/000086
Other languages
English (en)
Chinese (zh)
Inventor
Qian Li
Manji Sun
Ailing Fu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Pharmacology and Toxicology of AMMS
Original Assignee
Institute of Pharmacology and Toxicology of AMMS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Institute of Pharmacology and Toxicology of AMMS filed Critical Institute of Pharmacology and Toxicology of AMMS
Publication of WO2005071071A1 publication Critical patent/WO2005071071A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1025—Acyltransferases (2.3)
    • C12N9/1029—Acyltransferases (2.3) transferring groups other than amino-acyl groups (2.3.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • the present invention relates to a transduction peptide-human choline acetyltransferase fusion protein and a nucleic acid molecule containing a nucleotide sequence encoding the fusion protein.
  • the present invention also relates to an expression vector containing the aforementioned nucleic acid molecule.
  • the invention also relates to the use of the fusion protein for preparing a medicine for treating neurodegenerative disease or preventing Alzheimer's disease, promoting learning and memory function, and promoting intelligence.
  • the present invention particularly relates to a pharmaceutical composition containing the fusion protein, which can be administered by various methods such as injection, sublingual administration, lung aspiration, nasal mucosa, anal plug, or skin absorption. Background of the invention
  • the fusion protein was injected in mice and found that Active enzyme molecules are expressed in various tissues in the body, and it is particularly important that short peptides can carry large molecules across the blood-brain barrier.
  • the transduction peptide is an arginine-rich polypeptide.
  • the ability of TAT to cross the cell membrane automatically is due to the role of a peptide YGRKKRRQRRRGG (SEQ ID NO: 1) located on the TAT protein at positions 47-57.
  • the human-derived choline acetyltransferase used to construct the fusion protein contains the amino group of SEQ ID NO: 3 or a functional fragment thereof.
  • the human-derived choline acetyl acyltransferase consists of SEQ ID NO: 3.
  • the nucleotide sequence encoding the human choline acetyltransferase is shown in SEQ ID NO: 4.
  • the transduction peptide-human choline acetyltransferase fusion protein constructed according to the present invention has the amino acid sequence of SEQ ID NO: 5 or a functionally equivalent variant thereof.
  • the amino group of the functionally equivalent variant of the fusion protein is derived from a conservative modification of the amino acid sequence described in SEQ ID NO: 5 without substantially altering the function of the fusion protein, including the modification of the fusion protein. Substitution, addition or deletion of one or more conservative amino acid residues in an amino acid sequence.
  • the prokaryotic expression fusion protein constructed by the present invention When the prokaryotic expression fusion protein constructed by the present invention is transferred into a cell, it is refolded under the action of a chaperone molecule to restore the natural conformation, so that ChAT can exert its biological activity, and the protein transduction domain linked to it does not affect the cell. Normal structure or function.
  • Example 2 Expression and purification of transduction peptide-CHAT fusion protein
  • E. coli BL21 E. coli Ul (DE3) pLysS was purchased from Beijing Tianwei Times Company
  • the transduction peptide-CHAT fusion protein was induced to be expressed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Psychiatry (AREA)
  • Microbiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne une protéine de fusion PTD (domaine de transduction de protéine)-choline acétyltransférase humaine et la molécule d'acide nucléique contenant la séquence nucléotidique codant la protéine de fusion, elle concerne également le vecteur d'expression comprenant la molécule d'acide nucléique précitée. De plus, l'invention concerne l'application de ladite protéine de fusion dans la préparation de médicaments destinée à traiter les maladies neurodégénératives ou à prévenir la maladie d'Alzheimer, à augmenter la mémoire d'apprentissage et à améliorer l'état du cerveau. Cette invention concerne également tout particulièrement une composition de médicaments renfermant la protéine de fusion, laquelle peut être employée par des méthodes multiples telles que l'injection, la médication sublinguale, l'absorption pulmonaire et imbibition des muqueuses respiratoires, par suppositoire ou sur la peau.
PCT/CN2005/000086 2004-01-20 2005-01-19 Proteine de fusion ptd-choline acetyltransferase humaine et son application Ceased WO2005071071A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CNA2004100025132A CN1648135A (zh) 2004-01-20 2004-01-20 转导肽－人源胆碱乙酰基转移酶融合蛋白及其应用
CN200410002513.2 2004-01-20

Publications (1)

Publication Number Publication Date
WO2005071071A1 true WO2005071071A1 (fr) 2005-08-04

Family

ID=34800345

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2005/000086 Ceased WO2005071071A1 (fr) 2004-01-20 2005-01-19 Proteine de fusion ptd-choline acetyltransferase humaine et son application

Country Status (2)

Country Link
CN (1) CN1648135A (fr)
WO (1) WO2005071071A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118542931A (zh) * 2024-07-30 2024-08-27 上海桀蒙生物技术有限公司 生物制品及其使用方法和应用

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100387623C (zh) * 2005-05-20 2008-05-14 福州大学 连接蛋白转导结构域及辅助蛋白的生物活性蛋白、它的制备方法和应用
CN1978466B (zh) * 2005-12-06 2011-07-20 中国人民解放军军事医学科学院毒物药物研究所 转导肽-人脑源性神经营养因子融合蛋白及其应用
CN101121751B (zh) * 2006-08-10 2012-04-11 中国人民解放军军事医学科学院毒物药物研究所 Ptd-酪氨酸羟化酶催化区域融合蛋白及其应用
CN101591640B (zh) * 2008-05-30 2013-05-01 上海转基因研究中心 一种利用穿透型干细胞转录因子诱导体细胞重编程的方法
CN101921314B (zh) * 2010-06-28 2012-11-21 华中科技大学 脑靶向防治老年性痴呆的神经营养因子融合多肽及制备方法
CN103864937A (zh) * 2012-12-13 2014-06-18 吴江近岸蛋白质科技有限公司 一种用于小rna转染的重组融合蛋白及其制备方法
CN107760696B (zh) * 2016-08-17 2021-07-02 中国人民解放军军事医学科学院毒物药物研究所 编码人胆碱乙酰转移酶或其融合蛋白的核酸序列及其用途
KR101971092B1 (ko) * 2017-06-28 2019-04-23 한국세라믹기술원 아세틸콜린수용체 결합 펩타이드

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996015806A1 (fr) * 1994-11-23 1996-05-30 Human Genome Sciences, Inc. Choline-acetylase humaine
WO2000062067A1 (fr) * 1999-02-28 2000-10-19 Washington University Nouvelles molecules de transduction et leurs procedes d'utilisation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996015806A1 (fr) * 1994-11-23 1996-05-30 Human Genome Sciences, Inc. Choline-acetylase humaine
WO2000062067A1 (fr) * 1999-02-28 2000-10-19 Washington University Nouvelles molecules de transduction et leurs procedes d'utilisation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118542931A (zh) * 2024-07-30 2024-08-27 上海桀蒙生物技术有限公司 生物制品及其使用方法和应用

Also Published As

Publication number Publication date
CN1648135A (zh) 2005-08-03

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