Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides

A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a seri...

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Autores principales: Wang, Nan, Xie, Gang, Liu, Chao, Cong, Wei, He, Shipeng, Li, Yinghua, Fan, Li, Hu, Hong-Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758422/
https://www.ncbi.nlm.nih.gov/pubmed/33363118
http://dx.doi.org/10.3389/fchem.2020.616147
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author Wang, Nan
Xie, Gang
Liu, Chao
Cong, Wei
He, Shipeng
Li, Yinghua
Fan, Li
Hu, Hong-Gang
author_facet Wang, Nan
Xie, Gang
Liu, Chao
Cong, Wei
He, Shipeng
Li, Yinghua
Fan, Li
Hu, Hong-Gang
author_sort Wang, Nan
collection PubMed
description A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a series of all-hydrocarbon stapled peptides derivatives of A4K14-citropin 1.1 were designed and synthesized, and their chemical and biological characteristics were also investigated. Among them, A4K14-citropin 1.1-Sp1 and A4K14-citropin 1.1-Sp4 displayed improved helicity levels, greater protease stability, and increased antitumor activity compared with the original peptide, which establishes them as promising lead compounds for novel cancer therapeutics development. These results revealed the important influence of all-hydrocarbon stapling side chain on the secondary structure, hydrolase stability, and biological activity of A4K14-citropin 1.1.
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spelling pubmed-77584222020-12-25 Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides Wang, Nan Xie, Gang Liu, Chao Cong, Wei He, Shipeng Li, Yinghua Fan, Li Hu, Hong-Gang Front Chem Chemistry A4K14-citropin 1.1 is a structurally optimized derivative derived from amphibians' skin secreta peptide Citropin, which exhibits broad biological activities. However, the application of A4K14-citropin 1.1 as a cancer therapeutic is restricted by its structural flexibility. In this study, a series of all-hydrocarbon stapled peptides derivatives of A4K14-citropin 1.1 were designed and synthesized, and their chemical and biological characteristics were also investigated. Among them, A4K14-citropin 1.1-Sp1 and A4K14-citropin 1.1-Sp4 displayed improved helicity levels, greater protease stability, and increased antitumor activity compared with the original peptide, which establishes them as promising lead compounds for novel cancer therapeutics development. These results revealed the important influence of all-hydrocarbon stapling side chain on the secondary structure, hydrolase stability, and biological activity of A4K14-citropin 1.1. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7758422/ /pubmed/33363118 http://dx.doi.org/10.3389/fchem.2020.616147 Text en Copyright © 2020 Wang, Xie, Liu, Cong, He, Li, Fan and Hu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Wang, Nan
Xie, Gang
Liu, Chao
Cong, Wei
He, Shipeng
Li, Yinghua
Fan, Li
Hu, Hong-Gang
Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title_full Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title_fullStr Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title_full_unstemmed Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title_short Design, Synthesis, and Antitumor Activities Study of Stapled A4K14-Citropin 1.1 Peptides
title_sort design, synthesis, and antitumor activities study of stapled a4k14-citropin 1.1 peptides
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758422/
https://www.ncbi.nlm.nih.gov/pubmed/33363118
http://dx.doi.org/10.3389/fchem.2020.616147
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