Liquid Droplet Formation and Facile Cytosolic Translocation of IgG in the Presence of Attenuated Cationic Amphiphilic Lytic Peptides — ASN Events
  1. Schedule
  2. SESSION 7: Peptide permeability and delivery
  3. Liquid Droplet Formation and Facile Cytosolic Translocation of IgG in the Presence of Attenuated Cationic Amphiphilic Lytic Peptides

Liquid Droplet Formation and Facile Cytosolic Translocation of IgG in the Presence of Attenuated Cationic Amphiphilic Lytic Peptides (#32)

Takahiro Iwata 1 , Hisaaki Hirose 1 , Junya Michibata 1 , Yoshimasa Kawaguchi 1 , Kentarou Sakamoto 1 , Shiroh Futaki 1
  1. Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan

We previously reported an attenuated cationic amphiphilic lytic (ACAL) peptide, engineered from a natural hemolytic peptide, named L17E [1]. Substantial cytosolic delivery of biomacromolecules, including immunoglobulin G (IgG), was attained in the presence of this peptide. Fc region binding peptide conjugated with L17E trimer [FcB(L17E)3] was designed for more efficient IgG delivery into cells [2]. Particle-like liquid droplets were generated by mixing Alexa Fluor 488 labeled IgG (Alexa488-IgG) with FcB(L17E)3. Droplet contact with the cellular membrane led to spontaneous influx and distribution of Alexa488-IgG throughout cells in serum containing medium. Involvement of cellular machinery accompanied by actin polymerization and membrane ruffling was suggested for the translocation. Alexa488-IgG negative charges were crucial in liquid droplet formation with positively charged FcB(L17E)3. Successful intracellular delivery of Alexa Fluor 594-labeled anti-nuclear pore complex antibody allowed binding to cellular targets in the presence of FcB(L17E)3. Conjugation of L17E to hydrophilic polymers was also found to provide a similar mode of cytosolic IgG delivery, suggesting design flexibility for intracellular delivery via liquid droplet (or coacervate).

 

  1. [1] Akishiba et al. Nat. Chem. 2017, 9, 751-761. [2] Iwata et al. Angew. Chem. Int. Ed. 2021, 60, 19804-19812.
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