Cargando…
Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers
Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs....
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380766/ https://www.ncbi.nlm.nih.gov/pubmed/37511527 http://dx.doi.org/10.3390/ijms241411768 |
_version_ | 1785080276986101760 |
---|---|
author | Tsuchiya, Keisuke Horikoshi, Kanako Fujita, Minami Hirano, Motoharu Miyamoto, Maho Yokoo, Hidetomo Demizu, Yosuke |
author_facet | Tsuchiya, Keisuke Horikoshi, Kanako Fujita, Minami Hirano, Motoharu Miyamoto, Maho Yokoo, Hidetomo Demizu, Yosuke |
author_sort | Tsuchiya, Keisuke |
collection | PubMed |
description | Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable α-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery. |
format | Online Article Text |
id | pubmed-10380766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103807662023-07-29 Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers Tsuchiya, Keisuke Horikoshi, Kanako Fujita, Minami Hirano, Motoharu Miyamoto, Maho Yokoo, Hidetomo Demizu, Yosuke Int J Mol Sci Article Cell-penetrating peptides (CPPs) are widely used for the intracellular delivery of a variety of cargo molecules, including small molecules, peptides, nucleic acids, and proteins. Many cationic and amphiphilic CPPs have been developed; however, there have been few reports regarding hydrophobic CPPs. Herein, we have developed stapled hydrophobic CPPs based on the hydrophobic CPP, TP10, by introducing an aliphatic carbon side chain on the hydrophobic face of TP10. This side chain maintained the hydrophobicity of TP10 and enhanced the helicity and cell penetrating efficiency. We evaluated the preferred secondary structures, and the ability to deliver 5(6)-carboxyfluorescein (CF) as a model small molecule and plasmid DNA (pDNA) as a model nucleotide. The stapled peptide F-3 with CF, in which the stapling structure was introduced at Gly residues, formed a stable α-helical structure and the highest cell-membrane permeability via an endocytosis process. Meanwhile, peptide F-4 demonstrated remarkable stability when forming a complex with pDNA, making it the optimal choice for the efficient intracellular delivery of pDNA. The results showed that stapled hydrophobic CPPs were able to deliver small molecules and pDNA into cells, and that different stapling positions in hydrophobic CPPs can control the efficiency of the cargo delivery. MDPI 2023-07-21 /pmc/articles/PMC10380766/ /pubmed/37511527 http://dx.doi.org/10.3390/ijms241411768 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tsuchiya, Keisuke Horikoshi, Kanako Fujita, Minami Hirano, Motoharu Miyamoto, Maho Yokoo, Hidetomo Demizu, Yosuke Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title | Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title_full | Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title_fullStr | Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title_full_unstemmed | Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title_short | Development of Hydrophobic Cell-Penetrating Stapled Peptides as Drug Carriers |
title_sort | development of hydrophobic cell-penetrating stapled peptides as drug carriers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380766/ https://www.ncbi.nlm.nih.gov/pubmed/37511527 http://dx.doi.org/10.3390/ijms241411768 |
work_keys_str_mv | AT tsuchiyakeisuke developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT horikoshikanako developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT fujitaminami developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT hiranomotoharu developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT miyamotomaho developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT yokoohidetomo developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers AT demizuyosuke developmentofhydrophobiccellpenetratingstapledpeptidesasdrugcarriers |