TY - JOUR
T1 - Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage
AU - Kim, Hyungjin
AU - Kitamatsu, Mizuki
AU - Ohtsuki, Takashi
N1 - Funding Information:
This work was supported by Okayama Foundation for Science and Technology , Japan.
Publisher Copyright:
© 2017 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP–cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim. Contribution of bioreducible linkage of dimeric TatBim towards apoptotic activity was also confirmed.
AB - Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP–cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim. Contribution of bioreducible linkage of dimeric TatBim towards apoptotic activity was also confirmed.
KW - Apoptosis
KW - Bioreducible linkage
KW - Cell-penetrating peptide
KW - Intracellular delivery
KW - Multivalency
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U2 - 10.1016/j.bmcl.2017.12.035
DO - 10.1016/j.bmcl.2017.12.035
M3 - Article
C2 - 29275934
AN - SCOPUS:85038828455
SN - 0960-894X
VL - 28
SP - 378
EP - 381
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 3
ER -