Abstract
A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells. To promote escape of the entrapped TatBim-RB molecules, cells were irradiated with ultrasound, which successfully induced endosomal escape and cytoplasmic dispersion of TatBim-RB, and subsequently apoptosis. Our results suggest that this peptide-sonosensitizer conjugate strategy may facilitate numerous kinds of medicinal chemistry studies, and furthermore, this specific conjugate may exhibit potential as a novel therapeutic agent for the promotion of apoptosis.
| Original language | English |
|---|---|
| Pages (from-to) | 4212-4217 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 25 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Aug 1 2017 |
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Keywords
- Apoptosis
- Cell-penetrating peptide
- Endosomal escape
- Sonosensitizer
- Ultrasound
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate. / Inaba, Yuki; Watanabe, Kazunori; Kitamatsu, Mizuki; Nakata, Eiji; Harada, Atsushi; Ohtsuki, Takashi.
In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 15, 01.08.2017, p. 4212-4217.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate
AU - Inaba, Yuki
AU - Watanabe, Kazunori
AU - Kitamatsu, Mizuki
AU - Nakata, Eiji
AU - Harada, Atsushi
AU - Ohtsuki, Takashi
PY - 2017/8/1
Y1 - 2017/8/1
N2 - A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells. To promote escape of the entrapped TatBim-RB molecules, cells were irradiated with ultrasound, which successfully induced endosomal escape and cytoplasmic dispersion of TatBim-RB, and subsequently apoptosis. Our results suggest that this peptide-sonosensitizer conjugate strategy may facilitate numerous kinds of medicinal chemistry studies, and furthermore, this specific conjugate may exhibit potential as a novel therapeutic agent for the promotion of apoptosis.
AB - A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells. To promote escape of the entrapped TatBim-RB molecules, cells were irradiated with ultrasound, which successfully induced endosomal escape and cytoplasmic dispersion of TatBim-RB, and subsequently apoptosis. Our results suggest that this peptide-sonosensitizer conjugate strategy may facilitate numerous kinds of medicinal chemistry studies, and furthermore, this specific conjugate may exhibit potential as a novel therapeutic agent for the promotion of apoptosis.
KW - Apoptosis
KW - Cell-penetrating peptide
KW - Endosomal escape
KW - Sonosensitizer
KW - Ultrasound
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UR - http://www.scopus.com/inward/citedby.url?scp=85021106366&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2017.06.024
DO - 10.1016/j.bmc.2017.06.024
M3 - Article
C2 - 28647135
AN - SCOPUS:85021106366
VL - 25
SP - 4212
EP - 4217
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 15
ER -