2. Academic Validation
  3. Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

  • Bioorg Med Chem Lett. 2020 Sep 1;30(17):127362. doi: 10.1016/j.bmcl.2020.127362.
Yohei Nomura 1,  Kentarou Sakamoto 1,  Misao Akishiba 1,  Takahiro Iwata 1,  Hisaaki Hirose 1,  Shiroh Futaki 2
Affiliations

Affiliations

  • 1 Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
  • 2 Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. Electronic address: futaki@scl.kyoto-u.ac.jp.
PMID: 32738963 DOI: 10.1016/j.bmcl.2020.127362
Abstract

Intracellular delivery of biomacromolecules is a challenging research field in chemical biology and drug delivery. We previously reported a peptide named L17E, which successfully delivered functional proteins, including antibodies, into cells. However, relatively high concentrations of L17E and proteins are needed. In this study, we prepared dimers of L17E and its analog L17E/Q21E. Dimerization of L17E increased cytotoxicity leading to reduced intracellular delivery compared with L17E. On the Other hand, the dimers of the L17E analog, L17E/Q21E, especially when tethered at the N-termini, yielded a comparable level of intracellular delivery with L17E at decreased amounts of delivery peptides and cargoes.

Keywords

Antibody; Attenuated lytic peptides; Biopharmaceutical; Dimerization; Intracellular delivery.

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