L17E – Cell Penetrating Peptides – CPP

L17E is an endosomolytic peptide derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin and contains a substitution of leucine by glutamic acid at position 17. L17E is able to promote the endocytic uptake and cytosolic delivery of exosome-encapsulated proteins. A major obstacles to intracellular targeting by antibodies is the limited release of the antibodies into the cytosol, once inside endosomes. L17E can achieve an enhanced cellular uptake via the induction of micropinocytosis. Once inside the endosome, positively charged L17E is able to preferentially disrupt negatively charged endosomal membranes to enable a marked cytosolic liberation of antibodies (immunoglobulins G (IgGs)) from endosomes. L17E had little pH dependence and no enhanced helical structure is needed for L17E-mediated membrane lysis.