α/β-Peptides as Nanomolar Triggers of Lipid Raft-Mediated Endocytosis through GM1 Ganglioside Recognition

Abstract

Cell delivery of therapeutic macromolecules and nanoparticles is a critical drug development challenge. Translocation through lipid raft-mediated endocytic mechanisms is being sought, as it can avoid rapid lysosomal degradation. Here, we present a set of short α/β-peptide tags with high affinity to the lipid raft-associated ganglioside GM1. These sequences induce effective internalization of the attached immunoglobulin cargo. The structural requirements of the GM1-peptide interaction are presented, and the importance of the membrane components are shown. The results contribute to the development of a receptor-based cell delivery platform.

Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

“…Analogously to conventional α‐CPPs, β‐peptides and α/β‐hybrids have also shown the ability to permeate the plasma membrane following both direct penetration and endocytosis 222,223 …”

“…221 Analogously to conventional α-CPPs, β-peptides and α/β-hybrids have also shown the ability to permeate the plasma membrane following both direct penetration and endocytosis. 222,223 Moreover, the resistance of β-peptides toward degradation by proteases made them promising candidates for the development of antimicrobic peptides. Specifically, synthesizing β-peptide analogs of active yet protease-sensitive α-peptides has proved to be a promising strategy.…”