Potentiating the Membrane Interaction of an Attenuated Cationic Amphiphilic Lytic Peptide for Intracellular Protein Delivery by Anchoring with Pyrene Moiety

We previously reported an approach for intracellular protein delivery by attenuating membrane-lytic activity of cationic amphiphilic peptides on cell surfaces. HAad is one such that cytosolically delivers proteins interest, including antibodies, stimulating their endosomal escape. Additionally, elicits ruffling membrane, accompanied transient membrane permeabilization, allowing the efficient cytosolic translocation proteins. In this study, we prepared a conjugate with pyrenebutyric acid as membrane-anchoring unit (pBu-HAad). pBu-HAad demonstrated into cells only 1/20 concentration HAad. However, conjugates cholesteryl hemisuccinate and aliphatic fatty acids (C = 3, 6, 10) did not yield marked effects. The results time-course inhibitor studies suggest anchoring pyrene moiety leads to enhanced peptide–membrane interaction loosen lipid packing, thus facilitating through membranes.