Amyloid fibrillar oligomer conformational epitope polypeptide and application thereof

A technology of amyloid protein and antibody, applied in the biological field, can solve problems such as patient death, achieve the effect of eliminating side effects and good immunogenicity

Inactive Publication Date: 2012-06-20
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, unfortunately in the second phase of clinical trials, although most of the patients still showed good

Method used

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  • Amyloid fibrillar oligomer conformational epitope polypeptide and application thereof
  • Amyloid fibrillar oligomer conformational epitope polypeptide and application thereof
  • Amyloid fibrillar oligomer conformational epitope polypeptide and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0049] Embodiment 1, the preparation of polypeptide PEOS and derivative thereof and antibody

[0050] 1. Obtaining Peptide PEOS

[0051] The present invention uses phage display technology, with the polyclonal antibody OC (Millipore, USA, catalog number AB2286) that specifically recognizes fibrous oligomers and fibers as a screening substrate, and 1 × 10 8 A circular heptapeptide was panned for four rounds, and phage clones that could significantly bind to OC were screened by phage ELISA, and obtained by amino acid sequencing. Polypeptide PEOS, its amino acid sequence is: Cys-Trp-Thr-Thr-His-Gln-Arg-Ser-Cys (sequence 1, CWTTHQRSC)

[0052] The synthetic preparation method of PEOS is:

[0053] PEOS is a cyclic peptide, plus 2 cysteines at both ends to form a 9-peptide, which can be artificially synthesized and prepared by Shanghai Gil Biochemical Co., Ltd. according to conventional methods (see Weng C C, Peter D W. Fmoc Solid Phase Peptide for the preparation method Synthesi...

Embodiment 2

[0070] Embodiment 2, the application of polypeptide PEOS and its antibody

[0071] 1. Application of PEOS antibody

[0072] 1. Binding of PEOS antibody to various amyloid fibrillar oligomers and fibers

[0073] The purchased Aβ42 (American Peptide Co., catalog number 62-0-80B), amylin (American Peptide Co., catalog number 74-5-14B), α-synuclein (American rpeptide, catalog number No. S-1001-2), PrP (American Peptide Co., catalog No. 62-0-07B) were treated as follows: dissolved in hexafluoroisopropanol (HFIP) to 1 mg / ml, at room temperature (25°C) Sonicate for 10 minutes, dispense into epidorf tubes, volatilize HFIP in a vacuum environment, and store at -20°C. Before use, place the HFIP-treated Aβ42, amylin, and α-synuclein at room temperature for 20 minutes, add dimethyl sulfoxide (DMSO) to make the concentration of each protein 5 mg / ml, and then use 0.02M PBS buffer solution with pH 7.4 Dilute to desired concentration. PrP was prepared directly with 0.02M pH 7.4 PBS to the...

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Abstract

The invention discloses an amyloid fibrillar oligomer conformational epitope polypeptide and application of the amyloid fibrillar oligomer conformational epitope polypeptide. The polypeptide provided by the invention is a protein (1) or (2) as follows: the polypeptide (1) has an amino acid sequence shown in SEQ ID NO.1 in the sequence table, and the polypeptide (2) is derived from the polypeptide (1) by replacement and/or deletion and/or insertion of one or more amino acid residues in the amino acid sequence of SEQ ID NO.1 in the sequence table and has the same function as the polypeptide (1). The studies show that the polypeptide and antibodies thereof have the following benefits: the polypeptide can effectively stimulate production of a specific antibody against amyloid fibrillar oligomer in vivo, and the antibody can inhibit aggregation and cytotoxicity of amyloid, improve space memory in experimental animals, and reduce content of senile plaques and/or content of amyloid-beta (A-beta) in the brain.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to an amyloid fibrous oligomer conformation type antigen epitope polypeptide and its application. Background technique [0002] In recent years, various diseases caused by the aggregation of amyloid or polypeptide itself have caused more and more harm to human health. Some proteins themselves are non-toxic or have very little toxicity, but they themselves can aggregate into oligomers (oligomer) or fibrils (fibril) with toxic effects and cause a series of diseases, such as Beta-amyloid (A-Beta) Alzheimer's disease (Alzheimer's disease, AD), caused by alpha-synuclein (Parkinson's disease, PD), caused by prion protein (Prion protein (PrP)), including At least ten kinds of encephalopathy in humans and animals including mad cow disease, at least nine kinds of hereditary neurodegenerative diseases including Huntington's disease caused by polyglutamine (PolyQ)-containing polypeptides, caused ...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K16/18A61K38/08A61K39/395A61P25/28
Inventor 刘瑞田孙晓霞赵敏
Owner TSINGHUA UNIV
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