A reversible cell penetrating peptide-cargo linkage allows dissection of cell penetrating peptide- and cargo-dependent effects on internalization and identifies new functionalities of putative endolytic peptides.

ABSTRACT: Cell penetrating peptides (CPPs) are a promising technology for therapeutic delivery of macromolecular cargos. CPPs have generally used covalent linkages to cargo, ensuring a common fate as one molecule. Conversely, our CPP-adaptor, TAT-CaM, noncovalently binds calmodulin binding sequence (CBS)-containing cargos in calcium rich media then dissociates in the calcium-poor endosomal environment following internalization, enhancing endosomal escape relative to standard CPPs. In this study, we report cell entry of positively charged protein cargos that were not increased by TAT-CaM while cargos based on the negatively charged maltose binding protein (MBP) displayed little intrinsic internalization but were internalized by TAT-CaM. In addition, association of positively charged proteins with neg

SUBMITTER: Morris DP 

PROVIDER: S-EPMC9720253 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature