Receptor-Mediated Shuttling of a D-Amino Acid Peptide Achieves High Nanomolar Cytosolic Concentrations.

ABSTRACT: Delivery of therapeutic peptides and proteins to the cytosol is of great interest due to their ability to inhibit intracellular protein-protein interactions, which are mostly deemed undruggable by small molecules. Internalization into the endosomal pathway is possible by receptor-targeted approaches; however, endosomal escape is inefficient, and its quantification is challenging. To improve our current understanding of cytosolic delivery, we performed comprehensive studies on a receptor-mediated shuttle system based on the chemokine-like receptor 1 (CMKLR1). As a model cargo, PMIγ was used, a known D-amino acid peptide antagonist of the MDM2/p53 interaction, which survives the harsh conditions in the endocytic pathway. Fluorescence correlation spectroscopy (FCS) was used to demonstrate tha

SUBMITTER: List M 

PROVIDER: S-EPMC12814185 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature