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Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide

PURPOSE: Aurein 1.2 (Aur) peptide is known for possessing anticancer characteristics devoid of conventional therapeutics side effects. For improving Aur peptide anticancer functionality, different anticancer peptides were constructed based on Aur peptide through targeting two separate strategies, in...

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Autores principales: Salarpour Garnaie, Hamta, Shahabi, Arman, Geranmayeh, Mohammad Hossein, Barzegar, Abolfazel, Yari Khosroushahi, Ahmad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tabriz University of Medical Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460806/
https://www.ncbi.nlm.nih.gov/pubmed/37646048
http://dx.doi.org/10.34172/apb.2023.063
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author Salarpour Garnaie, Hamta
Shahabi, Arman
Geranmayeh, Mohammad Hossein
Barzegar, Abolfazel
Yari Khosroushahi, Ahmad
author_facet Salarpour Garnaie, Hamta
Shahabi, Arman
Geranmayeh, Mohammad Hossein
Barzegar, Abolfazel
Yari Khosroushahi, Ahmad
author_sort Salarpour Garnaie, Hamta
collection PubMed
description PURPOSE: Aurein 1.2 (Aur) peptide is known for possessing anticancer characteristics devoid of conventional therapeutics side effects. For improving Aur peptide anticancer functionality, different anticancer peptides were constructed based on Aur peptide through targeting two separate strategies, including (1) sequence-based mutations and (2) adding a cell-penetrating peptide linker. METHODS: The study was approached by designing three different analogs of Aur, including (a) Aur mutant (Aur(m)), (b) Aur with N-terminal polyarginine linker (R5-Aur), and (c) Aur(m) with R5 (R5-Aur(m)). Computational molecular dynamics simulations clearly showed higher structural stability of R5-Aur and R5-Aur(m) compared to Aur, solely. The α-helical properties of R5-Aur and R5-Aur(m) were protected during 500 ns simulations in water solution while no such structural conservation was seen for Aur in silico. RESULTS: The results of the current study highlight response to one of the main challenges of cancer therapy through selective invasion of Aur to cancer cells without significant involvement of normal cells. This issue was confirmed by different assays, including: MTT assay, flow cytometry, qPCR, and nuclei morphological observations. Furthermore, this study intensifies exploiting in silico approaches for adjusting drug delivery. The results of different assessments on designed peptides reveal an anticancer activity pattern rising from Aur toward Aur(m), and R5- Aur, consecutively. CONCLUSION: The designed structure of Aur shows improved anticancer activity through molecular changes which makes it suggestable for anticancer therapies.
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spelling pubmed-104608062023-08-29 Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide Salarpour Garnaie, Hamta Shahabi, Arman Geranmayeh, Mohammad Hossein Barzegar, Abolfazel Yari Khosroushahi, Ahmad Adv Pharm Bull Research Article PURPOSE: Aurein 1.2 (Aur) peptide is known for possessing anticancer characteristics devoid of conventional therapeutics side effects. For improving Aur peptide anticancer functionality, different anticancer peptides were constructed based on Aur peptide through targeting two separate strategies, including (1) sequence-based mutations and (2) adding a cell-penetrating peptide linker. METHODS: The study was approached by designing three different analogs of Aur, including (a) Aur mutant (Aur(m)), (b) Aur with N-terminal polyarginine linker (R5-Aur), and (c) Aur(m) with R5 (R5-Aur(m)). Computational molecular dynamics simulations clearly showed higher structural stability of R5-Aur and R5-Aur(m) compared to Aur, solely. The α-helical properties of R5-Aur and R5-Aur(m) were protected during 500 ns simulations in water solution while no such structural conservation was seen for Aur in silico. RESULTS: The results of the current study highlight response to one of the main challenges of cancer therapy through selective invasion of Aur to cancer cells without significant involvement of normal cells. This issue was confirmed by different assays, including: MTT assay, flow cytometry, qPCR, and nuclei morphological observations. Furthermore, this study intensifies exploiting in silico approaches for adjusting drug delivery. The results of different assessments on designed peptides reveal an anticancer activity pattern rising from Aur toward Aur(m), and R5- Aur, consecutively. CONCLUSION: The designed structure of Aur shows improved anticancer activity through molecular changes which makes it suggestable for anticancer therapies. Tabriz University of Medical Sciences 2023-07 2022-12-06 /pmc/articles/PMC10460806/ /pubmed/37646048 http://dx.doi.org/10.34172/apb.2023.063 Text en ©2023 The Authors. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers.
spellingShingle Research Article
Salarpour Garnaie, Hamta
Shahabi, Arman
Geranmayeh, Mohammad Hossein
Barzegar, Abolfazel
Yari Khosroushahi, Ahmad
Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title_full Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title_fullStr Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title_full_unstemmed Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title_short Designing Potent Anticancer Peptides by Aurein 1.2 Key Residues Mutation and Catenate Cell-Penetrating Peptide
title_sort designing potent anticancer peptides by aurein 1.2 key residues mutation and catenate cell-penetrating peptide
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460806/
https://www.ncbi.nlm.nih.gov/pubmed/37646048
http://dx.doi.org/10.34172/apb.2023.063
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