A synthetic peptide that readily penetrates the blood-brain barrier

A technique for synthesizing peptides and ischemic stroke, applied in the field of biomedicine, can solve the problems of large doses, severe side effects, and limited clinical application, achieve small side effects, improve oxidative stress damage, improve cognitive dysfunction and dementia effect

Active Publication Date: 2019-09-17
WUHAN HONGYUE MEDICAL SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although both glycine and cysteine ​​have obvious brain protective effects, the peripheral doses of glycine (800mg / kg) and cysteine ​​(500mg / kg) are too large, resulting in severe side effects, which limit their clinical application

Method used

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  • A synthetic peptide that readily penetrates the blood-brain barrier
  • A synthetic peptide that readily penetrates the blood-brain barrier
  • A synthetic peptide that readily penetrates the blood-brain barrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] [Example 1] This patent takes L-phenylalanine-L-cysteine-glycine tripeptide (FCG) as an example to illustrate the preparation process of solid-phase synthetic peptides as follows:

[0056] 1. Synthesis of Complex I Fmoc-Gly-resin:

[0057] The tripeptide of this patent uses the method of solid-phase synthesis, weighs 10.7g of 2-chlorotrityl chloride resin (2-Chlorotrityl Chloride Resin) with a degree of substitution of 0.4mmol / g, puts the resin into a polypeptide reaction tube, and adds Dichloromethane (DCM) 160.5ml, shaken for 30 minutes; filter the DCM solvent through a sand core, add 12mmol of Fmoc-Gly-OH amino acid, and then add 40mmol of N,N-diisopropylethylamine (DIEA), Finally, a small amount of dimethylformamide (DMF) was added to dissolve, and shaken for 1 h. Alternately wash 6 times with DMF and DCM. Add 160.5ml of 20% piperidine (piperidine is dissolved in DMF solution), take out the piperidine after 5 minutes, add 160.5ml of 20% piperidine again, wait for ...

Embodiment 2

[0075] [Example 2] Cytotoxicity test of the patent synthetic peptide on primary cortical neurons

[0076] In this example, the primary cortical neurons cultured for 10 days were used as the experimental object to establish an isolated glucose-oxygen deprivation (OGD) model of cortical neurons. In the case of OGD injury, the neurons were treated with 500 μM of each synthetic peptide. Use cck8 to evaluate the viability of cells, so as to judge whether each synthetic peptide has a protective effect on neurons. The synthetic peptide used in this embodiment is as follows:

[0077] Table 1 The synthetic peptides involved in this embodiment

[0078]

[0079]

[0080] 1. Main experimental reagents and instruments

[0081] Each synthetic peptide in the experiment was independently synthesized by our laboratory; Neurobasal, provided by Gibco; B27, provided by Gibco; FBS, provided by Invitrogen; glutamax, provided by Invitrogen; Glutamicacid, provided by sigma; , provided by sig...

Embodiment 3

[0101] [Example 3] Establish a rat cerebral ischemia model, inject fluorescently labeled synthetic peptides intravenously, and observe the ability of the synthetic peptides to penetrate the blood-brain barrier as a whole

[0102] 1. The main reagents and instruments of the experiment

[0103] FITC, Wuhan Minghao Biotechnology Co., Ltd.; FITC-CG, FITC-CGF, FITC-CGPF, Wuhan Minghao Biotechnology Co., Ltd.; OCT glue, Beijing Zhongshan Jinqiao Biotechnology Co., Ltd.; pathological tissue slicer, Germany Leitz , Type 1512; fluorescence microscope, Ningbo Sunny Instrument Co., Ltd.; paraformaldehyde, Sinopharm Chemical Reagent Co., Ltd.

[0104] 2. Experimental principle

[0105] FITC (fluorescein isothiocyanate): It is yellow or orange-yellow crystalline powder with a molecular weight of 389.4, a maximum absorption wavelength of 490-495nm, and a maximum emission wavelength of 520-530nm, showing bright yellow-green fluorescence. The broadest fluorescein.

[0106] FITC-CGPF: CGPF ...

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Abstract

The invention belongs to the technical field of biological medicine and particularly relates to synthetic peptide and an application of the same in preparing drugs in treatment of brain injuries. The amino acid sequence of the synthetic peptide is X1-(L-Cys-Gly)n-X2-X3-X4-X5, wherein, X1 is null or L-Phe, X2 is null or L-Pro, X3 is null or Gly, X4 is null or L-Cys, X5 is null or L-Phe, and X1 and X5 cannot be null at the same time; when X2 and X3 are null, n is smaller than or equal to 8, when X2 is L-Pro and X3 and X4 are null, n is smaller than or equal to 8, and when X2 is L-Pro and X3 is Gly, n is smaller than or equal to 7. Animal experiment shows that the synthetic peptide of the kind can pass the brain-blood barrier by means of intravenous administration at very low doses and generate unbonded glycine and cysteine in a hydrolysis manner under the action of protein hydrolysis enzyme in the brain to play a role of neuroprotection, ischemia perfusion damage of the brain is reduced, and the purpose of treating brain stroke is achieved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a synthetic peptide and its application in preparing medicine for treating brain injury. Background technique [0002] Glycine is the amino acid with the simplest chemical structure, but it has complex functions. Glycine is an important inhibitory neurotransmitter in the central nervous system, playing an important role in controlling neuronal excitability. Animal experiments have found that glycine has obvious neuroprotective effects, and it has also been found in some clinical trials that glycine can significantly improve cognitive dysfunction and dementia, especially as a conventional neuroleptic for the treatment of schizophrenia. In addition to this, glycine can also treat heart damage and stroke. [0003] L-cysteine ​​is a neuromodulatory substance and an antioxidant with neuroprotective effects. At the same time, it is also an important synthesis unit of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/083C07K5/087C07K5/103C07K5/107C07K7/06C07K7/08A61K38/06A61K38/07A61K38/08A61K38/10A61P9/10A61P25/00A61P25/28A61P25/16
Inventor 万芪陈娟庄杨张娅万沙
Owner WUHAN HONGYUE MEDICAL SCI INC
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