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Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy

Antimicrobial peptides (AMPs) are a class of molecules that play an essential role in innate immune regulation. The Brevinin-1 family are AMPs that show strong pharmacological and antimicrobial potential. A novel peptide, B1A, was designed based on the primary structure of brevinin-1PLb and brevinin...

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Autores principales: He, Haoyang, Chen, Yuqing, Ye, Zhuming, Chen, Xiaoling, Ma, Chengbang, Zhou, Mei, Xi, Xinping, Burrows, James F., Chen, Tianbao, Wang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464788/
https://www.ncbi.nlm.nih.gov/pubmed/32781587
http://dx.doi.org/10.3390/biology9080209
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author He, Haoyang
Chen, Yuqing
Ye, Zhuming
Chen, Xiaoling
Ma, Chengbang
Zhou, Mei
Xi, Xinping
Burrows, James F.
Chen, Tianbao
Wang, Lei
author_facet He, Haoyang
Chen, Yuqing
Ye, Zhuming
Chen, Xiaoling
Ma, Chengbang
Zhou, Mei
Xi, Xinping
Burrows, James F.
Chen, Tianbao
Wang, Lei
author_sort He, Haoyang
collection PubMed
description Antimicrobial peptides (AMPs) are a class of molecules that play an essential role in innate immune regulation. The Brevinin-1 family are AMPs that show strong pharmacological and antimicrobial potential. A novel peptide, B1A, was designed based on the primary structure of brevinin-1PLb and brevinin-1PLc. Subsequently, a synthesised replicate was subjected to a series of bioassays and was found to display antimicrobial activity. However, it also displayed high levels of haemolysis in a horse red blood cell haemolytic assay, suggesting potential toxicity. Therefore, we rationally designed a number of B1A analogues with aim of retaining antimicrobial activity, lowering toxicity, and to explore the structure–activity relationship of its N-terminus. B1A and its analogues still retained the “Rana Box” and the FLP-motif, which is a feature of this subfamily. However, the introduction of Lys and Trp residues into the peptide sequences revealed that antimicrobial activity of these analogues remained unchanged once the hydrophobicity and the charge reached the threshold. Hence, the idea that the hydrophobicity saturation in different situations is related to antimicrobial activity can be understood via the structure–activity relationship. Meanwhile, it could also be the starting point for the generation of peptides with specific antimicrobial activity.
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spelling pubmed-74647882020-09-04 Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy He, Haoyang Chen, Yuqing Ye, Zhuming Chen, Xiaoling Ma, Chengbang Zhou, Mei Xi, Xinping Burrows, James F. Chen, Tianbao Wang, Lei Biology (Basel) Article Antimicrobial peptides (AMPs) are a class of molecules that play an essential role in innate immune regulation. The Brevinin-1 family are AMPs that show strong pharmacological and antimicrobial potential. A novel peptide, B1A, was designed based on the primary structure of brevinin-1PLb and brevinin-1PLc. Subsequently, a synthesised replicate was subjected to a series of bioassays and was found to display antimicrobial activity. However, it also displayed high levels of haemolysis in a horse red blood cell haemolytic assay, suggesting potential toxicity. Therefore, we rationally designed a number of B1A analogues with aim of retaining antimicrobial activity, lowering toxicity, and to explore the structure–activity relationship of its N-terminus. B1A and its analogues still retained the “Rana Box” and the FLP-motif, which is a feature of this subfamily. However, the introduction of Lys and Trp residues into the peptide sequences revealed that antimicrobial activity of these analogues remained unchanged once the hydrophobicity and the charge reached the threshold. Hence, the idea that the hydrophobicity saturation in different situations is related to antimicrobial activity can be understood via the structure–activity relationship. Meanwhile, it could also be the starting point for the generation of peptides with specific antimicrobial activity. MDPI 2020-08-06 /pmc/articles/PMC7464788/ /pubmed/32781587 http://dx.doi.org/10.3390/biology9080209 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
He, Haoyang
Chen, Yuqing
Ye, Zhuming
Chen, Xiaoling
Ma, Chengbang
Zhou, Mei
Xi, Xinping
Burrows, James F.
Chen, Tianbao
Wang, Lei
Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title_full Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title_fullStr Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title_full_unstemmed Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title_short Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy
title_sort modification and targeted design of n-terminal truncates derived from brevinin with improved therapeutic efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464788/
https://www.ncbi.nlm.nih.gov/pubmed/32781587
http://dx.doi.org/10.3390/biology9080209
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