Discovery of a Macropinocytosis‐Inducing Peptide Potentiated by Medium‐Mediated Intramolecular Disulfide Formation
- 24 February 2021
- journal article
- research article
- Published by Wiley in Angewandte Chemie
- Vol. 60 (21), 11928-11936
- https://doi.org/10.1002/anie.202016754
Abstract
Macropinocytosis is among ubiquitous cellular uptake mechanisms of peptide‐based intracellular delivery. Due to its capability of engulfing large macromolecules, macropinocytosis shows promise as a route for the intracellular uptake of biomacromolecules and nanoparticles. We previously reported SN21, a peptide derived from the N‐terminus of stromal cell‐derived growth factor 1α (SDF‐1α), as a potent macropinocytosis inducer. In this work, we obtained the 8‐residue analog P4A bearing higher macropinocytosis induction ability. P4A contains vital cysteine residues in its sequence, which immediately reacts with cystine in culture medium to convert into its oxidized forms, including the intramolecularly oxidized form (oxP4A) as the dominant and active species. The conjugate of oxP4A with membrane lytic peptide LK15 delivered bioactive proteins into cells; notably, this peptide delivered functional proteins fused with a negatively charged protein tag at a significantly reduced amount (up to nanomolar range) without compromising the delivery efficiency and the cellular activities of delivered proteins.Funding Information
- Japan Society for the Promotion of Science (JP18H04403, JP18H04017)
- Core Research for Evolutional Science and Technology (JPMJCR18H5)
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