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Preparation and application of ischemic myocardial targeted mitochondria-directed peptide compound

A technique for targeting peptides and mitochondria, applied in the field of biomedicine, can solve the problems of decreased activity of mitochondrial electron transport chain complexes, decreased mitochondrial DNA transcription regulation function, increased mitochondrial matrix volume, etc. Application value, effect of increasing effectiveness

Pending Publication Date: 2021-11-12
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mitochondrial structure and dysfunction, mainly manifested by mitochondrial volume expansion, increased ridge area, and increased mitochondrial matrix volume, in addition, reduced activity of mitochondrial electron transport chain complexes, increased intramitochondrial calcium accumulation, accompanying these changes Mitochondrial DNA transcription Regulatory function will also decrease

Method used

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  • Preparation and application of ischemic myocardial targeted mitochondria-directed peptide compound
  • Preparation and application of ischemic myocardial targeted mitochondria-directed peptide compound
  • Preparation and application of ischemic myocardial targeted mitochondria-directed peptide compound

Examples

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preparation example Construction

[0037] The invention provides a method for preparing a mitochondrial targeting peptide complex, comprising the following steps:

[0038] Step 1: Combining TPPh3, namely 5-carboxypentyl-triphenylphosphonium bromide, with cardiomyocyte targeting peptide CSTSMLKAC to chemically synthesize TPP + + CSTSMLKAC targeting peptide;

[0039] Step 2: Use the tissue mitochondrial isolation kit to isolate and purify mitochondria;

[0040] Step 3: Dissolve the dissolved TPP ++CSTSMLKAC guide peptide resuspended purified mitochondrial pellet, incubate on shaker at 4°C for 20 minutes in the dark, then incubate at 4°C for 20 minutes to allow mitochondria and TPP + +CSTSMLKAC guide peptide is fully combined to form mitochondria-TPP-CSTSMLKAC guide peptide complex, after centrifugation, resuspend with phosphate buffer to a concentration of 7.5-10×10 4 pc / ml mitochondrial suspension, keep it on ice for later use.

[0041] The invention provides a TPP + Use of targeting peptides combined with ...

Embodiment

[0053] as attached figure 1 : It is a schematic diagram of the technical route of the mitochondria-TPP+CSTSMLKAC complex of the present invention for treating ischemic myocardial injury through vein transplantation.

[0054] 1. Combining TPPh3 (TPPh3=5-carboxypentyl-triphenylphosphine bromide) with cardiac targeting peptide CSTSMLKAC to chemically synthesize TPP+CSTSMLKAC targeting peptide, and dissolving it in PBS at 10 mg / ml to prepare TPP+CSTSMLKAC targeting peptide suspension .

[0055] 2. Obtain the myocardium of mitochondria-specific green fluorescent mice, use a tissue mitochondrial isolation kit to separate and purify mitochondria (Beyond Biotechnology Co., Ltd., C3606), and resuspend the purified mitochondrial pellet with dissolved TPP+CSTSMLKAC targeting peptide to avoid Incubate on a shaker at 4°C for 20 minutes, then incubate at 4°C for 20 minutes to fully combine mitochondria with TPP+CSTSMLKAC targeting peptide to form: mitochondria-TPP-CSTSMLKAC targeting pepti...

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Abstract

The invention relates to preparation and application of an ischemic myocardial targeted mitochondria-directed peptide compound, and belongs to the technical field of biological medicines. According to the invention, mitochondria recognition molecules and ischemic myocardial cell targeting peptides are combined and react with active mitochondria to form a mitochondria-TPP + CSTSMLKAC compound, and ischemic myocardial injury is treated through vein transplantation; the guiding peptide CSTSMLKAC can guide mitochondria to a myocardial ischemia area, damaged myocardial cells enhance self energy metabolism by taking in exogenous mitochondria, mechanical contraction and relaxation functions of myocardial energy dependent myocardial cells are improved, damage caused by myocardial cell apoptosis is inhibited, and heart failure is delayed; and after vein transplantation of the mitochondria-TPP + CSTSMLKAC compound, the cardiac dysfunction can be relieved. A mitochondrial transplantation approach can be remarkably simplified through vein transplantation of mitochondria, the application cost of mitochondrial transplantation is reduced, and the ischemic myocardial targeted mitochondria-directed peptide compound has important clinical popularization and application value.

Description

technical field [0001] The invention relates to the preparation and application of a mitochondria-guiding peptide complex targeting ischemic myocardium, and belongs to the technical field of biomedicine. Background technique [0002] Mitochondria play an important role in the maintenance of cell homeostasis and function. As a highly oxygen-consuming organelle, mitochondrial dysfunction will directly affect cell function and eventually lead to organ dysfunction. The heart, as an organ with high energy demands, has a stronger dependence on mitochondria. The 30% ratio of mitochondria in cardiomyocytes also shows the importance of mitochondria to cardiomyocytes from the perspective of development or evolution. Mitochondria can produce 30 kg of ATP per day to maintain normal cardiac mechanical function. Mitochondria provide protection for cardiomyocyte systolic and diastolic function through oxidative phosphorylation. Mitochondrial structure and dysfunction, mainly manifested...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/107A61K9/00A61K31/66A61K47/64A61P9/00A61P9/04A61P9/10
CPCC07K7/06A61K31/66A61K47/64A61K9/0019A61P9/04A61P9/00A61P9/10
Inventor 孙爱军葛均波孙晓垒高日峰陈航黄涯曲亚男马雷雷
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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