Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

Yohei Nomura; Kentarou Sakamoto; Misao Akishiba; Takahiro Iwata; Hisaaki Hirose; Shiroh Futaki

doi:10.1016/j.bmcl.2020.127362

Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

Yohei Nomura, Kentarou Sakamoto, Misao Akishiba, Takahiro Iwata, Hisaaki Hirose, Shiroh Futaki

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Article number	127362
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2020.127362
Publication status	Published - Sept 1 2020
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2020.127362

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title = "Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides",

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.",

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T1 - Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

AU - Nomura, Yohei

AU - Sakamoto, Kentarou

AU - Akishiba, Misao

AU - Iwata, Takahiro

AU - Hirose, Hisaaki

AU - Futaki, Shiroh

PY - 2020/9/1

Y1 - 2020/9/1

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AB - 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.

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Improved cytosolic delivery of macromolecules through dimerization of attenuated lytic peptides

Abstract

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