There is a pressing need to develop ways to deliver therapeutic macromolecules to intracellular targets. The mammalian cell membrane is a major obstacle in drug development because it represents a barrier that is mostly impermeable to extracellular proteins that can potentially act as specific, and tolerable drugs. Therefore, effective degradation-free intracellular protein delivery at therapeutically relevant extracellular/serum concentrations (low nM) is among the most important current challenges in drug development and chemistry. Degradation-free endocytosis can also occur through the lipid raft-mediated/caveolar pathway, which is exploited by viruses and bacterial toxins for cellular entry. Our research group discovered a pentapeptidic tag WYKYW and a macromolecular assembly with this segment, which can route macromolecular cargoes to the degradation free lipid raft-mediated endocytic pathway at therapeutically relevant extracellular concentrations. This result defines a new class of delivery systems: the endocytosis routing sequences, which is based on a specific lipid raft receptor – peptide interaction.

Selected publications

α/β-Peptides as Nanomolar Triggers of Lipid Raft-Mediated Endocytosis through GM1 Ganglioside Recognition. Hetényi, A.; Szabó, E.; Imre, N.; Bhaumik, K. N.; Tököli, A.; Füzesi, T.; Hollandi, R.; Horvath, P.; Czibula, Á.; Monostori, É.; Deli, M. A.; Martinek, T. A. Pharmaceutics 2022, 14 (3).

Routing Nanomolar Protein Cargoes to Lipid Raft-Mediated/Caveolar Endocytosis through a Ganglioside GM1-Specific Recognition Tag.Imre, N.; Hetényi, A.; Szabó, E.; Bodnár, B.; Szkalisity, A.; Gróf, I.; Bocsik, A.; Deli, M. A.; Horvath, P.; Czibula, Á.; Monostori, É.; Martinek, T. A. Adv. Sci. 2020, 7 (4).

Endocytosis routing sequence peptide for cell delivery systems, European Patent office, EP3980439A1