Fatty acylation enhances the cellular internalization and cytosolic distribution of a cystine-knot peptide.

ABSTRACT: Delivering peptides into cells could open up possibilities for targeting intracellular proteins. Although fatty acylation of peptide therapeutics improves their systemic half-life, it remains unclear how it influences their cellular uptake. Here, we demonstrate that a fatty acylated peptide exhibits enhanced cellular internalization and cytosolic distribution compared to the un-acylated version. By using a cystine-knot peptide as a model system, we report an efficient strategy for site-specific conjugation of fatty acids. Peptides modified with fatty acids of different chain lengths entered cells through clathrin-mediated and macropinocytosis pathways. The cellular uptake was mediated by the length of the hydrocarbon chain, with myristic acid conjugates displaying the highest distribution

SUBMITTER: Gao X 

PROVIDER: S-EPMC8529511 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature