TAT-LBD-NEP1-40 fusion protein, construction method and application thereof

A fusion protein and protein sequence technology, applied in the field of protein transduction, can solve the problems of inability to concentrate and poor targeting of TAT protein, achieve the effects of reducing side effects, high transduction efficiency, and overcoming limitations

Inactive Publication Date: 2013-05-22
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Abstract
  • Description
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Problems solved by technology

However, the targeting of TAT protein is poor, and after entering the brain, it is widely distributed and cannot concentrate on the ischemic injury site.

Method used

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  • TAT-LBD-NEP1-40 fusion protein, construction method and application thereof
  • TAT-LBD-NEP1-40 fusion protein, construction method and application thereof
  • TAT-LBD-NEP1-40 fusion protein, construction method and application thereof

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Embodiment Construction

[0036] Drug efficacy test of TAT-LBD-NEP1-40 fusion protein

[0037] In order to prove the beneficial effects of the present invention, the inventors used the TAT-LBD-NEP1-40 fusion protein constructed in the present invention to conduct the following pharmacodynamic research, and the test conditions are as follows:

[0038] It should be noted that the experimental methods not specifying specific conditions in the following drug efficacy tests are usually according to conventional conditions such as Sambrook et al., molecular cloning: the conditions described in the laboratory manual (New York: Cold Spring Harbor Laboratory Press, 1989) and conditions described in David et al., Cell Experiment Guide (New York: Cold Spring Harbor Laboratory Press, 1998).

[0039] (1) Identification of transduction function of TAT-LBD-NEP1-40 fusion protein

[0040] 1. Identification of TAT-LBD-NEP1-40 fusion protein entering the brain through the blood-brain barrier

[0041] Nine SD rats were...

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Abstract

The invention discloses a TAT-LBD-NEP1-40 fusion protein, a construction method and an application thereof for treating central lesion. The TAT-LBD-NEP1-40 fusion protein constructed by the invention remains selective antagonistic activity of NEP1-40 to a Nogo receptor and has the advantages of high transduction efficiency and easy transmission of blood and spine barriers and blood brain barrier, so that the limit of NEP1-40 is overcome so as to avoid the deficiency of extra damage to nervous tissues caused by micro-injection of NEP1-40 or micro pump implantation and difficulty for NEP1-40 to pass through blood and spine barriers and blood brain barrier to meet corresponding biological concentration. The infusion protein provided by the invention can be massively prepared, and is low in cost and high in activity. The infusion protein can be used to treat various CNS (Central Nervous System) damages such as cerebral ischemia and anoxia, cerebral hemorrhage, cerebral trauma and spinal cord injury, promote regeneration of nervous tissues and neural functional recovery, and treat CNS damages.

Description

technical field [0001] The invention belongs to the field of protein transduction, in particular to introducing LBD into TAT-NEP1-40 fusion to prepare TAT-LBD-NEP1-40 fusion protein. At the same time, the invention also relates to the TAT-LBD-NEP1-40 fusion protein passing through the blood-brain barrier and being enriched in the ischemic area for the treatment of central nervous system injury. Background technique [0002] Trauma, stroke, cerebral hemorrhage, and spinal cord injury are characterized by high mortality and disability. How to reduce the degree of neurological damage and how to better improve the function of damaged neurons and improve the quality of life of patients is of great significance to patients, their families and society, and is a worldwide problem. Currently, there is no effective treatment for neurological dysfunction caused by CNS injury. Therefore, finding new and effective drugs for the treatment of brain CNS injury is a research hotspot. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62C12N15/70A61K38/17A61K47/48A61P25/00A61K47/64
Inventor 王强苟兴春李立亚熊利泽
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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