Discovery of a Macropinocytosis?Inducing Peptide Potentiated by Medium?Mediated Intramolecular Disulfide Formation

Macropinocytosis is a ubiquitous cellular uptake mechanism of peptide-based intracellular delivery. This entry pathway shows promise as route for the biomacromolecules and nanoparticles. In this work, we obtained 8-residue analogue P4A bearing higher macropinocytosis induction ability. contains vital cysteine residues in its sequence, which immediately reacts with cystine culture medium to convert into oxidized forms, including intramolecularly form (oxP4A) dominant active species. The conjugate oxP4A membrane lytic peptide LK15 delivered bioactive proteins cells; notably, functional fused negatively charged protein tag at significantly reduced amount (up nanomolar range) without compromising delivery efficiency activities proteins.