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One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide
[Image: see text] Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by alterin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979329/ https://www.ncbi.nlm.nih.gov/pubmed/36873017 http://dx.doi.org/10.1021/acsomega.2c06766 |
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author | Chang, Linlin Wu, Xiaoyan Ran, Kaixin Tian, Yali Ouyang, Xu Liu, Hui Gou, Sanhu Zhang, Yun Ni, Jingman |
author_facet | Chang, Linlin Wu, Xiaoyan Ran, Kaixin Tian, Yali Ouyang, Xu Liu, Hui Gou, Sanhu Zhang, Yun Ni, Jingman |
author_sort | Chang, Linlin |
collection | PubMed |
description | [Image: see text] Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by altering the charge shielding position of the anionic binding partner LE based on the cationic ACP LK and investigated their pH response, cytotoxic activity, and serum stability, in hoping to achieve a desirable acid-activatable ACP. As expected, the obtained hybrid peptides could be activated and exhibit a remarkable antitumor activity by rapid membrane disruption at acidic pH, whereas its killing activity could be alleviated at normal pH, showing a significant pH response compared with LK. Importantly, this study found that the peptide LK-LE3 with the charge shielding in the N-terminal of LK displayed notably low cytotoxicity and more stability, demonstrating that the position of charge masking is extremely important for the improvement of peptide toxicity and stability. In short, our work opens a new avenue to design promising acid-activated ACPs as potential targeting agents for cancer treatment. |
format | Online Article Text |
id | pubmed-9979329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-99793292023-03-03 One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide Chang, Linlin Wu, Xiaoyan Ran, Kaixin Tian, Yali Ouyang, Xu Liu, Hui Gou, Sanhu Zhang, Yun Ni, Jingman ACS Omega [Image: see text] Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by altering the charge shielding position of the anionic binding partner LE based on the cationic ACP LK and investigated their pH response, cytotoxic activity, and serum stability, in hoping to achieve a desirable acid-activatable ACP. As expected, the obtained hybrid peptides could be activated and exhibit a remarkable antitumor activity by rapid membrane disruption at acidic pH, whereas its killing activity could be alleviated at normal pH, showing a significant pH response compared with LK. Importantly, this study found that the peptide LK-LE3 with the charge shielding in the N-terminal of LK displayed notably low cytotoxicity and more stability, demonstrating that the position of charge masking is extremely important for the improvement of peptide toxicity and stability. In short, our work opens a new avenue to design promising acid-activated ACPs as potential targeting agents for cancer treatment. American Chemical Society 2023-02-20 /pmc/articles/PMC9979329/ /pubmed/36873017 http://dx.doi.org/10.1021/acsomega.2c06766 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Chang, Linlin Wu, Xiaoyan Ran, Kaixin Tian, Yali Ouyang, Xu Liu, Hui Gou, Sanhu Zhang, Yun Ni, Jingman One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title | One New Acid-Activated Hybrid Anticancer Peptide by
Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title_full | One New Acid-Activated Hybrid Anticancer Peptide by
Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title_fullStr | One New Acid-Activated Hybrid Anticancer Peptide by
Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title_full_unstemmed | One New Acid-Activated Hybrid Anticancer Peptide by
Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title_short | One New Acid-Activated Hybrid Anticancer Peptide by
Coupling with a Desirable pH-Sensitive Anionic Partner Peptide |
title_sort | one new acid-activated hybrid anticancer peptide by
coupling with a desirable ph-sensitive anionic partner peptide |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9979329/ https://www.ncbi.nlm.nih.gov/pubmed/36873017 http://dx.doi.org/10.1021/acsomega.2c06766 |
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