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.