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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...

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Autores principales: Chang, Linlin, Wu, Xiaoyan, Ran, Kaixin, Tian, Yali, Ouyang, Xu, Liu, Hui, Gou, Sanhu, Zhang, Yun, Ni, Jingman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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.
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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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