RAG8 – Cell Penetrating Peptides – CPP

RAG8 is a pepducin- a cell-penetrating palmitoylated peptide with a C-terminal NH2.- Palmitoyl is a 16-carbon aliphatic chain which enhances the hydrophobicity of the peptide, and therefore improves its penetration through lipid structures. The peptide sequence corresponds to a key regulatory sequence at the intracellular C-terminus of PAR4. This motif regulates calcium signalling and PAR4 interactions with the signalling protein-β-arrestin. RAG8 is a PAR4 antagonist that can attenuate calcium signalling and β-arrestin-1 and 2 recruitment to PAR4 which has been activated with the PAR4 agonist AYPGKF-NH2.Disrupting this PAR4/β-arrestin signalling pathway with RAG8 blocks PAR4 dependent platelet activation and reduces stability of blood clots.