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
alpha/beta-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.