Enhanced intracellular delivery of macromolecules by melittin derivatives mediated cellular uptake

[Display omitted] Sequential fragmentation of melittin allows the optimization of cell penetrating behavior of peptides and facilitates the intracellular delivery of macromolecules such as proteins. Various cell-penetrating peptides (CPPs) have been utilized as a promising tool for intracellular delivery of therapeutic macromolecules. In this study, hemolytic membrane-active peptide (Melittin) has been utilized for intracellular uptake of macromolecules by its sequential fragmentation. Among its fragmented derivatives, melittin(1-14) showed highly efficient delivery of proteins into HeLa cells, while maintaining their biological activities. The highest level of intracellular delivery was observed when ß-galactosidase and Cytochrome C were co-delivered with melittin(1-14). These data suggested that melittin(1-14) could be a useful adjuvant for the enhanced intracellular delivery of therapeutic macromolecules.