RRC ID 86117
Author Michibata J, Kawaguchi Y, Furuyama Y, Sasaki Y, Akiyoshi K, Futaki S.
Title Addition of Oligoarginine to a Membrane Permeabilizing Peptide M-Lycotoxin Facilitates Intracellular Antibody Infusion from Microcondensate.
Journal Bioconjug Chem
Abstract Coacervate-based intracellular delivery of biomacromolecules has attracted our attention due to the feasibility of easy condensation of the biomacromolecules and their controllable release. Our laboratory has developed a unique, coacervate-based delivery system that uses the conjugate of the polysaccharide pullulan with membrane-permeabilizing peptides, including L17E and M-lycotoxin. This system enables immunoglobulin G (IgG) antibodies labeled with the negatively charged fluorophore Alexa Fluor 488 to enter the cytosol directly through the plasma membrane. Cyotosolic IgG distribution is complete within a few minutes after infusion initiation, and infusion can be achieved in serum-containing medium. The purpose of this study was to refine this system to reduce the amount of antibody required while maintaining satisfactory delivery efficiencies. Therefore, pullulan conjugates with M-lytocoxin bearing two to eight arginine residues were designed to enhance the interaction of M-lycotoxin with the cell membrane. The conjugates were able to form microcondensates with Alexa Fluor 488 labeled IgGs. The addition of arginine residues improved the efficiency of cytosolic infusion and successfully reduced the amounts of both antibodies and pullulan-peptide conjugates required for the delivery.
Volume 36(7)
Pages 1494-1503
Published 2025-7-16
DOI 10.1021/acs.bioconjchem.5c00176
PMID 40600603
MeSH Animals Arginine* / chemistry Cell Membrane / metabolism Cell Membrane Permeability* / drug effects Glucans / chemistry Humans Immunoglobulin G* / administration & dosage Immunoglobulin G* / chemistry Peptides* / chemistry
IF 4.031
Resource
Human and Animal Cells A549(RCB3677) MIA Paca2(RCB2094)