Membrane-permeable derivatives converted intracellularly into active peptides

摘要

The present invention relates to membrane-permeable peptides which are intracellular agonists and/or antagonists of chemotactic factor receptors rendered hydrophobic through acylation and acetoxymethylation of their amine and acid functional groups. The modified peptides of the present invention are loaded into cells. The acetoxymethyl esters are cleaved by non-specific esterases rendering the peptides active in the intracellular compartments of the cells. The effects of the introduction of transformed specific peptides corresponding to intracellular regions common to the major chemokine receptors are illustrated. These peptides completely inhibited chemotactic factor and chemokine-induced calcium mobilization. Furthermore, leukocytes of mice intravenously injected with these peptides failed to migrate towards chemokines(IL-8).