TY - JOUR
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
N1 - Funding Information:
This work was supported by JSPS KAKENHI (Grant Numbers 18H04403 and 18H04017 ), and by JST CREST (Grant Number JPMJCR18H5 ). K.S. and M.A. are grateful for the JSPS Research Fellowship for Young Scientists.
Funding Information:
This study was funded by Shionogi & Co., Ltd.
Funding Information:
This work was supported by JSPS KAKENHI (Grant Numbers 18H04403 and 18H04017), and by JST CREST (Grant Number JPMJCR18H5). K.S. and M.A. are grateful for the JSPS Research Fellowship for Young Scientists.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
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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U2 - 10.1016/j.bmcl.2020.127362
DO - 10.1016/j.bmcl.2020.127362
M3 - Article
C2 - 32738963
AN - SCOPUS:85087014214
SN - 0960-894X
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 17
M1 - 127362
ER -