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Preparation method and drug application value of nerve growth factor mutant with low immunization side effects

A technology of nerve growth factor and mutants, applied in the field of regulation of immune system and nervous system drugs, cell biological effects, crystal structure of mouse nerve growth factor and lipid small molecule lysoPS complex, can solve problems such as side effects

Active Publication Date: 2013-06-19
INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the diversity of biological functions of NGF, its application as a drug may bring potential side effects, and its molecular biological mechanism is still being studied in depth

Method used

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  • Preparation method and drug application value of nerve growth factor mutant with low immunization side effects
  • Preparation method and drug application value of nerve growth factor mutant with low immunization side effects
  • Preparation method and drug application value of nerve growth factor mutant with low immunization side effects

Examples

Experimental program
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Effect test

Embodiment 1

[0024] 1. SPR assay to analyze the affinity between mouse nerve growth factor (mNGF) and various small lipid molecules

[0025] The small lipid molecules used in this example were purchased from Avanti polar lipids, Inc.

[0026] SPR experiments were performed using a GE Biocore 3000 instrument. When light passes from a medium with a high refractive index to a medium with a low refractive index, part of the light will be reflected on the contact surface. When the incident angle is larger than the critical angle, the light will be totally reflected. However, when the surface of the glass is covered with a thin layer of inert metal film (such as gold), the plasma (plasma) on the surface of the metal film vibrates, and part of the light will be "lost" on the metal film. When the wave vector of the incident light coincides with the frequency of the surface plasmons, the electrons "resonate", a phenomenon known as surface plasmon resonance. The incident angle at which the intens...

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Abstract

The invention relates to the technical field of biomedical engineering, in particular to a mouse nerve growth factor (mNGF) and a crystal structure and a cell biological effect of a lipid small molecule lysoPS composite. Key amino acids which are combined by the mNGF and the lysoPS are analyzed and determined by means of the crystal structure, namely, the 88th lysine, and the locus of the 88th lysine is mutated by means of a technology of site-directed mutagenesis. The research result shows that the combination capacity of the mNGF mutant with the lysoPS declines obviously, and the toxic and side effect on cells of the mNGF is reduced significantly. The invention provides the crystal structure of the composite, the structural characteristics of the lipid small molecule lysoPS, the preparation method of the mNGF mutant proteins and functions of the mNGF mutant proteins on regulation of drugs of an immunization system and a nervous system.

Description

Field of invention: [0001] The invention relates to the technical field of biomedical engineering, in particular to the crystal structure of the compound of mouse-derived nerve growth factor (mNGF) and lipid small molecule lysoPS and the cell biological effect of the compound. Specifically, the present invention determines the key amino acid for mNGF binding to lysoPS through crystal structure analysis, that is, the 88th lysine, and then uses site-directed mutagenesis to mutate the site, prepare mutant proteins and carry out cell experiments. The research results showed that the ability of the mNGF mutant protein to bind to lysoPS was significantly reduced, and its toxic side effects on cells were also significantly reduced. The invention provides the crystal structure of the complex, the structural characteristics of the lipid small molecule lysoPS, the preparation method of the mNGF mutant protein and its use in regulating immune system and nervous system medicine. Backgro...

Claims

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Application Information

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IPC IPC(8): C07K14/48A61K38/18A61P25/00
Inventor 江涛唐捷童琼周洪哲孙含丽
Owner INSITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
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