Polypeptide with effect of inhibiting activity of fibroblast growth factor receptor 3 and application thereof

A growth factor receptor and fibroblast technology, applied in the field of biopharmaceuticals, can solve the problems of delayed closure of epiphyseal growth plate, widening of hypertrophic cartilage area, and overgrowth of long bones, etc., and achieve simple preparation, small molecular weight, and low immunogenicity Effect

Inactive Publication Date: 2012-08-08
THE THIRD AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIV OF PLA
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  • Abstract
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Problems solved by technology

Previous studies have shown that FGFR3 gain-of-function gene mutations can inhibit the proliferation and differentiation of chondrocytes in the epiphyseal growth plate, causing a variety of skeletal development defects genetic diseases, such as achondroplasia (ACH), hypochondriac hypoplasia (HCH) and lethal osteodysplasia (TD), etc.; and FGFR3 loss-of-function gene mutations can lead to delayed closure of epiphyseal growth plate, widened hypertrophic cartilage area, and overgrowth of long bones, etc.
[0004] Although 23 FGFs have been discovered so far, there is no FGF that only specifically binds to FGFR3

Method used

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  • Polypeptide with effect of inhibiting activity of fibroblast growth factor receptor 3 and application thereof
  • Polypeptide with effect of inhibiting activity of fibroblast growth factor receptor 3 and application thereof
  • Polypeptide with effect of inhibiting activity of fibroblast growth factor receptor 3 and application thereof

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Embodiment Construction

[0020] In order to make the purpose, technical solution and advantages of the present invention clearer, the present invention will be described in detail below in conjunction with the accompanying drawings. For the experimental methods not specified in the examples, the conventional conditions are generally followed, such as the conditions described in the Molecular Cloning Experiment Guide (Third Edition, J. Sambrook et al.), or the conditions suggested by the manufacturer.

[0021] 1. Synthesis of polypeptide core1

[0022] Shanghai Huada Tianyuan Biotechnology Co., Ltd. was entrusted to use the standard Fmoc protocol to synthesize a polypeptide with the amino acid sequence Thr-Leu-Gly-Gln-Leu-Leu (TLGQLL, SEQ ID No.1) in solid phase, and named the polypeptide Core1. The purity of the synthetic peptide is higher than 95%, and it is stored at -70°C.

[0023] 2. ELISA method to detect the binding of peptide Core1 to the extracellular segment of FGFR3

[0024] Using the indi...

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Abstract

The invention discloses polypeptide with an effect of inhibiting activity of fibroblast growth factor receptor 3 (FGFR3). The polypeptide consists of an amino acid sequence shown by Thr-Leu-Gly-Gln-Leu-Leu, can be combined with specificity of an extracellular fragment of the FGFR3, has an obvious inhibition effect on the activity of the extracellular fragment of the FGFR3, has the advantages of low molecular weight, simplicity in preparation, easily controlled quality, low immunogenicity and the like, can be prepared into a medicament for preventing and controlling FGFR3 function enhanced diseases, and has potential good application prospect in prevention and treatment of the FGFR3 function enhanced diseases such as thanatophoric dysplasia and achondroplasia.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to an active polypeptide and its application in the field of pharmacy. Background technique [0002] Fibroblast growth factor receptor (FGFR) is a kind of transmembrane tyrosine kinase receptor with autophosphorylation activity, which binds to its corresponding ligand fibroblast growth factor (FGF) , Play an important role in the process of tissue organ development and injury repair. [0003] Four kinds of FGFRs have been found so far, namely FGFR1, FGFR2, FGFR3 and FGFR4. Among them, FGFR3 is a negative regulatory molecule that mediates endochondral ossification and plays an important role in bone development. Previous studies have shown that FGFR3 gain-of-function gene mutations can inhibit the proliferation and differentiation of chondrocytes in the epiphyseal growth plate, causing a variety of skeletal development defects genetic diseases, such as achondroplasia (ACH)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/08A61P19/08
Inventor 陈林金旻杜晓兰戚华兵苏楠谭乔燕谢杨丽罗凤涛杨京
Owner THE THIRD AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIV OF PLA
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