Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus
EeCentrocin 1 is a potent antimicrobial peptide isolated from the marine sea urchin Echinus esculentus . The peptide has a hetero‐dimeric structure with the antimicrobial activity confined in its largest monomer, the heavy chain (HC), encompassing 30 amino acid residues. The aim of the present study...
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Online Access: | https://hdl.handle.net/10037/17360 https://doi.org/10.1002/psc.3233 |
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ftunivtroemsoe:oai:munin.uit.no:10037/17360 2023-05-15T14:27:10+02:00 Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus Solstad, Runar Gjerp Johansen, Cecilie Stensvåg, Klara Strøm, Morten B. Haug, Tor 2019-12-04 https://hdl.handle.net/10037/17360 https://doi.org/10.1002/psc.3233 eng eng Wiley Journal of Peptide Science info:eu-repo/grantAgreement/RCN/BIOTEK2021/208546/Norway/eXploring the BIOactive PEPtide Space of arctic marine invertebrates/XBioPepS/ Solstad RG, Johansen C, Stensvåg K, Strøm mbs, Haug T. Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus. Journal of Peptide Science. 2019 FRIDAID 1765204 doi:10.1002/psc.3233 1075-2617 1099-1387 https://hdl.handle.net/10037/17360 openAccess Copyright 2019 The Author(s) VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710::Medical molecular biology: 711 VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711 Journal article Tidsskriftartikkel Peer reviewed publishedVersion 2019 ftunivtroemsoe https://doi.org/10.1002/psc.3233 2021-06-25T17:57:06Z EeCentrocin 1 is a potent antimicrobial peptide isolated from the marine sea urchin Echinus esculentus . The peptide has a hetero‐dimeric structure with the antimicrobial activity confined in its largest monomer, the heavy chain (HC), encompassing 30 amino acid residues. The aim of the present study was to develop a shorter drug lead peptide using the heavy chain of EeCentrocin 1 as a starting scaffold and to perform a structure‐activity relationship study with sequence modifications to optimize antimicrobial activity. The experiments consisted of 1) truncation of the heavy chain, 2) replacement of amino acids unfavourable for in vitro antimicrobial activity, and 3) an alanine scan experiment on the truncated and modified heavy chain sequence to identify essential residues for antimicrobial activity. The heavy chain of EeCentrocin 1 was truncated to less than half its initial size, retaining most of its original antimicrobial activity. The truncated and optimized lead peptide ( P6 ) consisted of the 12 N ‐terminal amino acid residues from the original EeCentrocin 1 HC sequence and was modified by two amino acid replacements and a C ‐terminal amidation. Results from the alanine scan indicated that the generated lead peptide ( P6 ) contained the optimal sequence for antibacterial activity, in which none of the alanine scan peptides could surpass its antimicrobial activity. The lead peptide ( P6 ) was also superior in antifungal activity compared to the other peptides prepared and showed minimal inhibitory concentrations (MICs) in the low micromolar range. In addition, the lead peptide ( P6 ) displayed minor haemolytic and no cytotoxic activity, making it a promising lead for further antimicrobial drug development. Article in Journal/Newspaper Arctic University of Tromsø: Munin Open Research Archive Journal of Peptide Science 26 2 |
institution |
Open Polar |
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University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
topic |
VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710::Medical molecular biology: 711 VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711 |
spellingShingle |
VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710::Medical molecular biology: 711 VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711 Solstad, Runar Gjerp Johansen, Cecilie Stensvåg, Klara Strøm, Morten B. Haug, Tor Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
topic_facet |
VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710::Medical molecular biology: 711 VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711 |
description |
EeCentrocin 1 is a potent antimicrobial peptide isolated from the marine sea urchin Echinus esculentus . The peptide has a hetero‐dimeric structure with the antimicrobial activity confined in its largest monomer, the heavy chain (HC), encompassing 30 amino acid residues. The aim of the present study was to develop a shorter drug lead peptide using the heavy chain of EeCentrocin 1 as a starting scaffold and to perform a structure‐activity relationship study with sequence modifications to optimize antimicrobial activity. The experiments consisted of 1) truncation of the heavy chain, 2) replacement of amino acids unfavourable for in vitro antimicrobial activity, and 3) an alanine scan experiment on the truncated and modified heavy chain sequence to identify essential residues for antimicrobial activity. The heavy chain of EeCentrocin 1 was truncated to less than half its initial size, retaining most of its original antimicrobial activity. The truncated and optimized lead peptide ( P6 ) consisted of the 12 N ‐terminal amino acid residues from the original EeCentrocin 1 HC sequence and was modified by two amino acid replacements and a C ‐terminal amidation. Results from the alanine scan indicated that the generated lead peptide ( P6 ) contained the optimal sequence for antibacterial activity, in which none of the alanine scan peptides could surpass its antimicrobial activity. The lead peptide ( P6 ) was also superior in antifungal activity compared to the other peptides prepared and showed minimal inhibitory concentrations (MICs) in the low micromolar range. In addition, the lead peptide ( P6 ) displayed minor haemolytic and no cytotoxic activity, making it a promising lead for further antimicrobial drug development. |
format |
Article in Journal/Newspaper |
author |
Solstad, Runar Gjerp Johansen, Cecilie Stensvåg, Klara Strøm, Morten B. Haug, Tor |
author_facet |
Solstad, Runar Gjerp Johansen, Cecilie Stensvåg, Klara Strøm, Morten B. Haug, Tor |
author_sort |
Solstad, Runar Gjerp |
title |
Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
title_short |
Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
title_full |
Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
title_fullStr |
Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
title_full_unstemmed |
Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus |
title_sort |
structure‐activity relationship studies of shortened analogues of the antimicrobial peptide eecentrocin 1 from the sea urchin echinus esculentus |
publisher |
Wiley |
publishDate |
2019 |
url |
https://hdl.handle.net/10037/17360 https://doi.org/10.1002/psc.3233 |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
Journal of Peptide Science info:eu-repo/grantAgreement/RCN/BIOTEK2021/208546/Norway/eXploring the BIOactive PEPtide Space of arctic marine invertebrates/XBioPepS/ Solstad RG, Johansen C, Stensvåg K, Strøm mbs, Haug T. Structure‐activity relationship studies of shortened analogues of the antimicrobial peptide EeCentrocin 1 from the sea urchin Echinus esculentus. Journal of Peptide Science. 2019 FRIDAID 1765204 doi:10.1002/psc.3233 1075-2617 1099-1387 https://hdl.handle.net/10037/17360 |
op_rights |
openAccess Copyright 2019 The Author(s) |
op_doi |
https://doi.org/10.1002/psc.3233 |
container_title |
Journal of Peptide Science |
container_volume |
26 |
container_issue |
2 |
_version_ |
1766300774019629056 |