Molecular Mechanisms Underlying Peptide‑Mediated Protein Delivery into Cells

 

Molecular Mechanisms Underlying Peptide‑Mediated Protein Delivery into Cells

 

Date: 7^th May, 2026 (Thursday)

Time: 4 - 5 pm (HKT)

 

Venue: Lecture Theatre P1, Chong Yuet Ming Chemistry Building

 

 

Graduate School of Pharmaceutical Sciences

Kyoto University

 

Ph.D. (1989) from Kyoto University. Served as Research Associate and Associate Professor at the University of Tokushima (1987–1997), and as a Postdoctoral Associate at Rockefeller University (1989–1991). Later appointed as Associate Professor and then Professor at Kyoto University (1997–2025); currently a Specially Appointed Professor at the Graduate School of Pharmaceutical Sciences, Kyoto University. His research focuses on bioactive peptides with unique functions such as membrane remodeling and intracellular delivery. Honors include the Pharmaceutical Society of Japan Award (2020), Akabori Memorial Award (2022), and Naito Foundation Award (2025). Vice President of the Pharmaceutical Society of Japan and the Japanese Peptide Society.

 

One of the major research interests of our group is the design of peptides for intracellular delivery of biomacromolecules and the elucidation of the molecular mechanisms underlying this process. Arginine-rich peptides, including the HIV-1 TAT peptide and octaarginine (R8), are well-known cell-penetrating peptides (CPPs) that enter cells via endocytosis or direct membrane penetration [1]. Peptide adsorption onto cell membranes has been considered a crucial initial step for membrane penetration, and our studies have highlighted the importance of lipid packing in this process [2]. We also developed a spider toxin–derived peptide, L17E, capable of delivering antibodies (IgG) into cells [3]. Particle-like coacervates or microcondensates were generated by mixing Alexa Fluor 488–labeled IgG (Alexa488-IgG) with a conjugate of an Fc region–binding peptide and an L17E trimer [FcB(L17E)₃] [4]. Upon contact with the cell membrane, these microcondensates rapidly infused Alexa488-IgG into cells, resulting in broad intracellular distribution. This process occurred within minutes and was accompanied by dynamic reorganization of F-actin and membrane structures. Comparable infusion behavior was observed for coacervates generated from Alexa488-IgG and L17E conjugated to pullulan [5,6], as well as from siRNA/mRNA and FcB(L17E)₃ [7]. In this seminar, I will discuss chemical and cell biological perspectives on the mechanisms underlying peptide-mediated intracellular delivery of functional biomolecules.

 

[1] S. Futaki, I. Nakase, Acc. Chem. Res. 2017, 50, 2449-2456

[2] T. Murayama et al., Angew. Chem. Int. Ed. 2017, 56, 7644-7647

[3] M. Akishiba et al., Nature Chem. 2017, 9, 751-761

[4] T. Iwata et al. Angew. Chem. Int. Ed. 2021, 60, 19804–19812

[5] J. Michibata et al. Bioconjug. Chem. 2024, 35, 1888–1899

[6] J. Michibata et al. Bioconjug. Chem. 2025, 36, 1494–1503

[7] Y. Kawaguchi et al. Angew. Chem. Int. Ed. 2026, 65, e12139

 

- - ALL ARE WELCOME - -