A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus

Yoshiyuki Hakata; Hiroyuki Michiue; Takashi Ohtsuki; Masaaki Miyazawa; Mizuki Kitamatsu

doi:10.1016/j.bmcl.2019.02.004

A leucine zipper-based peptide hybrid delivers functional Nanog protein inside the cell nucleus

Bioorg Med Chem Lett. 2019 Apr 1;29(7):878-881. doi: 10.1016/j.bmcl.2019.02.004. Epub 2019 Feb 4.

Authors

Yoshiyuki Hakata¹, Hiroyuki Michiue², Takashi Ohtsuki³, Masaaki Miyazawa⁴, Mizuki Kitamatsu⁵

Affiliations

¹ Department of Immunology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Sayama, Osaka 589-8511, Japan. Electronic address: hakata@med.kindai.ac.jp.
² Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
³ Department of Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
⁴ Department of Immunology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Sayama, Osaka 589-8511, Japan.
⁵ Department of Applied Chemistry, Faculty of Science and Engineering, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. Electronic address: kitamatu@apch.kindai.ac.jp.

PMID: 30737088
DOI: 10.1016/j.bmcl.2019.02.004

Abstract

We synthesized a pair of compounds containing leucine zipper peptides to deliver protein cargo into cells. One is a cell-penetrating peptide (CPP) with Lz(E), a leucine zipper peptide containing negatively charged amino acids, and the other is a Nanog protein with Lz(K), a leucine zipper peptide containing positively charged amino acids. When cells were treated with these equimolar mixtures, Nanog-Lz(K) hybridized with Lz(E)-CPP was successfully delivered into the cells. Furthermore, Nanog-Lz(K) exerted its proper function after nuclear transport.

Keywords: Cell-penetrating peptide; Drug delivery system; Leucine zipper; Nanog; Peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Cell Nucleus
Cell-Penetrating Peptides / chemistry*
Cell-Penetrating Peptides / pharmacology*
HeLa Cells
Humans
Leucine Zippers*
Nanog Homeobox Protein / metabolism*

Substances

Cell-Penetrating Peptides
Nanog Homeobox Protein