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Short peptide and immunosuppressant containing the same and application thereof

An immunosuppressant and short peptide technology, which is applied in the field of medicine, can solve the problems of difficult production, high production cost, and high price, and achieve the effect of short structure, low side effects, and inhibition of binding

Inactive Publication Date: 2010-10-27
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Therefore, the technical problem to be solved by the present invention is to provide a new drug for the treatment of autoimmune diseases in view of the existing problems of difficult production, high production cost and high price in the existing drugs for treating autoimmune diseases produced by antibodies , the drug can specifically antagonize the interaction between FcγRIIA and IgG, thereby preventing or treating autoimmune diseases caused by antibodies

Method used

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  • Short peptide and immunosuppressant containing the same and application thereof
  • Short peptide and immunosuppressant containing the same and application thereof
  • Short peptide and immunosuppressant containing the same and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0022] Design and synthesis of embodiment 1 short peptide sequence

[0023] After sequence design, optimization and screening, 9 short peptides were obtained, as shown in Table 1. Sent to Shanghai Jill Biochemical Synthesis, the purity was >95%, and used for the experiments in the following examples.

[0024] Table 1. Short peptides obtained through design and optimization

[0025]

Embodiment 2

[0026]Example 2 The short peptide compound of the present invention specifically antagonizes the interaction between FcγRIIA and IgG

[0027] The short peptides used are: No. 1-5 short peptides.

[0028] (1) Cell culture

[0029] U937 cells (purchased from the Cell Bank of Shanghai Chinese Academy of Sciences), using RMPI1640 culture medium containing 10% (v / v) calf serum, at 37 ° C, 5% (v / v) CO 2 to cultivate. K562 cells (purchased from the Shanghai Chinese Academy of Sciences Cell Bank), using IMDM culture medium containing 10% (v / v) fetal bovine serum, 100 U / ml penicillin and 100 μg / ml streptomycin, at 37 ° C, 5% (v / v )CO 2 to cultivate.

[0030] (2) Determination of short peptide compound antagonizing FcγRIIA-IgG interaction activity

[0031] The binding of FcγR and IgG on the cell surface was counted by flow cytometry.

[0032] Specific steps: Take cells in the doubling phase, wash 3 times with sterile PBS, and resuspend to 1×10 6 / ml. In the negative control grou...

Embodiment 3

[0039] Example 3 The short peptide can antagonize the binding between FcγRIIA-IgG in a concentration-dependent manner

[0040] The short peptide used is peptide No. 1.

[0041] (1) Cell culture

[0042] K562 cells were cultured in IMDM medium containing 10% (v / v) fetal bovine serum, 100 U / ml penicillin and 100 μg / ml streptomycin at 37°C in 5% (v / v) CO 2 to cultivate.

[0043] (2) CELL ELISA to verify the concentration-dependent antagonism of short peptides between FcγRIIA-IgG

[0044] The 96-well plate was blocked with 2% (w / v) PBS-B (2% (w / v) PBS-B, dissolved in 100ml PBS with 2g of bovine serum albumin (BSA), similar to the following), 4 ℃ overnight or at room temperature for 2h. The K562 cells in the logarithmic growth phase were washed 3 times with 1% (w / v) PBS-B. Resuspend K562 cells in 1% (w / v) PBS-B, adjust the concentration to 6×10 6 / ml, add 100 μl of K562 cells to each well, and remove the supernatant after centrifugation. The IgG group was directly added with...

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Abstract

The invention discloses short peptide and immunosuppressant containing the same and application thereof. The short peptide contains 6 peptides, and the amino acid sequence thereof is the combination in any order selected from any 6 amino acid residues of Thr, Pro, Ala, Ile, Phe, His, Trp, Tyr or Glu. The short peptide can be used for preparing medicine with the mutual action of an antagonism FcgammaIIA receptor (FcgammaRIIA) and immunoglobulin G (IgG) and medicine for preparing, curing or preventing autoimmune diseases, and is characterized by strong specificity, short structure, low immunogenicity and simple synthesis. The medicine with the short peptide can specifically resist the mutual action between FcgammaRIIA and IgG, but not resist the action between FcgammaRI and IgG, thereby having low side effect. The peptide will be widely applied in preparing novel immunosuppressant, and will bring huge social and economic benefits.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a short peptide, an immunosuppressant containing it and application thereof. Background technique [0002] Antibody-generated autoimmune diseases are a type of autoimmune diseases that cause tissue and cell damage due to the production of autoantibodies. It includes a variety of diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and anti-neutrophil antibody (Anti-Neutrophil Cytoplasmic Antibody, ANCA)-associated vasculitis. These diseases are a class of chronic progressive diseases with poor prognosis. In recent years, the pathogenesis of autoimmune diseases caused by antibody production has not been fully understood. However, some important receptors and cellular pathways play a key role in the development of autoimmune diseases caused by antibodies. For example, Fcγ receptor (Fcγ receptor, FcγR) is a bridge mediating humoral immunity...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P37/06
Inventor 陈楠张骥朱维良王伟铭俞海瑾陈永熙
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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