Hydrophobicity-tuned anion responsiveness underlies endosomolytic cargo delivery mediated by amphipathic vehicle peptides.

ABSTRACT: Peptide conformation can change subject to environment cues. This concept also applies to many cationic amphipathic peptides (CAPs) known to have cell membrane lytic or penetrative activities. Well-conditioned CAPs can match the properties of the target membrane to support their intended biological functions, e.g., intracellular cargo delivery; however, the intricacy in such conditioning surpasses our current understanding. Here we focused on hydrophobicity, a key biophysical property that dictates the membrane activity of CAPs, and applied a structure-function strategy to evolve a template peptide for endosomolytic cargo delivery. The template was subjected to iterative adjustment to balance hydrophobicity between its N-terminal linear and C-terminal helical domains. We demonstrate that t

SUBMITTER: Chen X 

PROVIDER: S-EPMC8639468 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature