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Polypeptide drug Athycaltide and application thereof

A drug and application technology, applied in the field of biopharmaceutical research and development, can solve problems such as difficult recovery of cardiac hypertrophy

Active Publication Date: 2018-05-18
中国医科大学
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  • Abstract
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Problems solved by technology

Under physiological conditions, this characteristic of CaMKII helps to maintain the stability of the heart beat rhythm; and in pathological cardiac hypertrophy, intracellular Ca 2+ Concentrations continued to rise, and we speculated that the autophosphorylation allosteric memory of CaMKII may lead to cardiomyocytes' response to intracellular Ca 2+ Pathological states such as elevated concentrations form "memory" and cause continuous development of myocardial hypertrophy and difficulty in recovering from pathological states

Method used

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  • Polypeptide drug Athycaltide and application thereof
  • Polypeptide drug Athycaltide and application thereof
  • Polypeptide drug Athycaltide and application thereof

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Embodiment Construction

[0029] 1. The present invention first proves that Ca in the process of cardiac hypertrophy 2+ / CaM / CaMKII plays a key role in the phosphorylation of Cav1.2 channel proteins:

[0030] 1. The cell and whole animal models of pathological cardiac hypertrophy were prepared by subcutaneous injection of ISO in rats. (1) Observe the morphology of the heart at different time points in each model. (2) Detect the protein expression levels of Cav1.2 channel, CaM, CaMKII and p-CaMKII in myocardial tissue, and determine the changes in the amount of each protein itself.

[0031] 2. The myocardial hypertrophic cell model was prepared by ISO stimulation of neonatal rat primary cardiomyocytes, and the co-localization of p-CaMKII and Cav1.2 channels in hypertrophic cardiomyocytes was observed by laser confocal experiments.

[0032] Through the above studies, the relationship between the phosphorylation status of CaMKII to Cav1.2, the combination of p-CaMKII and Cav1.2, the change of Cav1.2 pro...

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Abstract

The invention belongs to the field of biopharmaceutical research and development, and particularly relates to a polypeptide drug Athycaltide and an application thereof. The amino acid sequence of thepolypeptide drug Athycaltide is as shown in SEQ ID No. 1, SEQ ID No. 2 and SEQ ID No. 3. The polypeptide drug can inhibit Ca<2+> / CaM / CaMKII signal transduction pathways, can also function in preventing, delaying and treating occurrence and development of cardiac hypertrophy, and provides a new idea for treatment of pathological cardiac hypertrophy.

Description

technical field [0001] The invention belongs to the field of research and development of biological medicines, and in particular relates to a class of polypeptide medicine and its application in treating cardiac hypertrophy. Background technique [0002] Cardiac hypertrophy (CH) is an adaptive compensatory response of the heart to various cardiovascular stimuli, such as hemodynamic load, angiotensin, adrenaline, growth factors, etc. It can maintain cardiac output in the early stage, but , Pathological cardiac hypertrophy caused by long-term stress can develop into cardiac enlargement, heart failure, and sudden death. Clinically, pathological myocardial hypertrophy can be caused by various diseases such as hypertension, valvular heart disease, myocardial infarction or ischemia, genetic or diabetic coronary artery disease, and is an independent risk factor for cardiovascular diseases. Cardiac hypertrophy caused by disease is different from the reversible physiological hypertr...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P9/04
CPCA61K38/00C07K14/001
Inventor 郝丽英李菁媛李卓康泽王思奇
Owner 中国医科大学
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