Aug 1, 2017
Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate.
Bioorganic & medicinal chemistry
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- Volume
- 25
- Number
- 15
- First page
- 4212
- Last page
- 4217
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.bmc.2017.06.024
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
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.
- Link information
- ID information
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- DOI : 10.1016/j.bmc.2017.06.024
- ISSN : 0968-0896
- eISSN : 1464-3391
- Pubmed ID : 28647135
- Web of Science ID : WOS:000406022200028