Fig. 2.

Endosome disrupting peptides. A) Conformation-changing fusogenic peptide HA2 exhibits a random coil at neutral pH and adopts a α-helical conformation at lower pH. Adapted with permission from ref. [84]. Copyright 1994 National Academy of Sciences. B) A chemical structure-changing peptide made by CDM modification of the NH₂ groups in melittin (the N-terminus and the Lys side chains indicated by arrows). The membrane activity of melittin is abolished after the modification, but can be recovered in a weakly acidic environment of endosome where it refolds into a homotetramer and disrupts the endosome membrane by pore formation. C) The chemical structure PF6 with a stearyl modified N-terminus and four trifluoromethyl quinoline moieties added onto the TP10 backbone. D) Photo-induced endosomal escape by modifying CPPs with photosensitizers. Light excitation of the sensitizer triggers the generation of singlet oxygen (¹O₂), which lyses the endosome membrane for siRNA escape.