A short peptide mimicking the n-terminal of rhoe, derivatives and pharmaceutical use thereof in the treatment of cardiac hypertrophy

By mimicking the binding of the short peptide at the N-terminus of RhoE to WWP2, the autophagy pathway of cardiomyocytes is activated, overcoming the therapeutic limitations caused by the inhibition of autophagy by existing drugs, and achieving effective treatment of myocardial hypertrophy.

CN122255244APending Publication Date: 2026-06-23THE SIXTH AFFILIATED HOSPITAL OF XINJIANG MEDICAL UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
THE SIXTH AFFILIATED HOSPITAL OF XINJIANG MEDICAL UNIV
Filing Date
2026-03-14
Publication Date
2026-06-23

AI Technical Summary

Technical Problem

Existing anti-hypertrophic drugs inhibit myocardial autophagy by suppressing angiotensin II type 1 receptors, which limits their effectiveness in treating cardiac remodeling and fails to effectively remove intracellular pathogenic proteins, leaving a clinical treatment need.

Method used

It provides short peptides and their derivatives that mimic the N-terminus of RhoE, which can bind to CAV3 on the cardiomyocyte membrane, enter the cytoplasm through the CAV3 endocytosis pathway, activate the E3 ubiquitin ligase WWP2, promote the interaction between WWP2 and P62, activate selective autophagy, and clear misfolded proteins and damaged organelles.

Benefits of technology

It achieves highly efficient autophagy within cardiomyocytes, rapidly clears intracellular pathogenic proteins, inhibits cardiomyocyte hypertrophy, and improves the therapeutic effect of myocardial hypertrophy.

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Abstract

This invention discloses a short peptide and its derivatives that mimic the N-terminus of RhoE, and their pharmaceutical applications in the treatment of myocardial hypertrophy, belonging to the field of biomedical technology. This short peptide precisely mimics the amino acid sequence from position 1 to 20 of RhoE, specifically binding to the WW domain of WWP2 and competitively blocking the interaction between the N-Loop and C-Loop of its HECT domain. This causes the WWP2 conformation to change from a self-inhibited "closed" state to an activated "open" state, activating E3 ligase activity. The short peptide retains its binding ability to the cardiomyocyte membrane cavernin CAV3, allowing it to efficiently enter the cardiomyocyte cytoplasm via the cavernin endocytosis pathway, overcoming the deficiency of traditional drugs in clearing intracellular pathogenic proteins. Peptide derivatives constructed by fusing transmembrane peptides such as TAT ​​and T7 further improve intracellular delivery efficiency. Experiments have demonstrated that this short peptide and its derivatives can significantly promote WWP2 self-ubiquitination, enhance cardiomyocyte autophagic flux, clear intracellular pathogenic proteins, and effectively inhibit cardiomyocyte hypertrophy, making it suitable for the preparation of anti-myocardial hypertrophy drugs.
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