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Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury

Lung inflammation and injuries are major health problems. The SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) binds to Toll-like receptor-4 and exerts anti-inflammatory activity. In this study, we have determined the stability of the structure and structure–activity relationship of the SPA4...

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Autores principales: Chowdhury, Asif Alam, Rodgers, Karla, Godbole, Nachiket M., Awasthi, Shanjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282593/
https://www.ncbi.nlm.nih.gov/pubmed/37350860
http://dx.doi.org/10.1039/d3ra02918b
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author Chowdhury, Asif Alam
Rodgers, Karla
Godbole, Nachiket M.
Awasthi, Shanjana
author_facet Chowdhury, Asif Alam
Rodgers, Karla
Godbole, Nachiket M.
Awasthi, Shanjana
author_sort Chowdhury, Asif Alam
collection PubMed
description Lung inflammation and injuries are major health problems. The SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) binds to Toll-like receptor-4 and exerts anti-inflammatory activity. In this study, we have determined the stability of the structure and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury. The SPA4 peptide was maintained at different pH and temperatures, in solutions of different ionic strengths, and simulated lung fluids. The primary and secondary structure of the SPA4 peptide was determined by ultraviolet-visible (UV-VIS) and circular dichroism (CD) spectroscopy. The activity of the SPA4 peptide was determined by measurement of secreted levels of chemokine C–X–C motif ligand 1/keratinocyte-derived chemokine (CXCL1/KC) and lactate by primary mouse lung epithelial cells against lipopolysaccharide (LPS) stimuli. Our results demonstrate the stability of the structure of the SPA4 peptide at room temperature and 4 °C over 10 days. The original UV-VIS spectra of the SPA4 peptide followed a typical pattern when incubated in solutions of pH 5.7, 7.0, and 8.0 at different temperatures, simulated lung fluids, and most of the chemical components. Slight shifts in the absorbance peaks, derivative values, and vibrational fine structures were noted in the fourth-derivative spectra of the SPA4 peptide under some conditions. An increased level of lactate is the hallmark of lung injury. The SPA4 peptide on its own and in the presence of lactate exerts anti-inflammatory activity. The primary and secondary structure and the activity of the SPA4 peptide remain intact when pre-incubated in 2 mM sodium lactate solution. The results provide important insights about the stability and structure–activity relationship of the SPA4 peptide.
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spelling pubmed-102825932023-06-22 Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury Chowdhury, Asif Alam Rodgers, Karla Godbole, Nachiket M. Awasthi, Shanjana RSC Adv Chemistry Lung inflammation and injuries are major health problems. The SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) binds to Toll-like receptor-4 and exerts anti-inflammatory activity. In this study, we have determined the stability of the structure and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury. The SPA4 peptide was maintained at different pH and temperatures, in solutions of different ionic strengths, and simulated lung fluids. The primary and secondary structure of the SPA4 peptide was determined by ultraviolet-visible (UV-VIS) and circular dichroism (CD) spectroscopy. The activity of the SPA4 peptide was determined by measurement of secreted levels of chemokine C–X–C motif ligand 1/keratinocyte-derived chemokine (CXCL1/KC) and lactate by primary mouse lung epithelial cells against lipopolysaccharide (LPS) stimuli. Our results demonstrate the stability of the structure of the SPA4 peptide at room temperature and 4 °C over 10 days. The original UV-VIS spectra of the SPA4 peptide followed a typical pattern when incubated in solutions of pH 5.7, 7.0, and 8.0 at different temperatures, simulated lung fluids, and most of the chemical components. Slight shifts in the absorbance peaks, derivative values, and vibrational fine structures were noted in the fourth-derivative spectra of the SPA4 peptide under some conditions. An increased level of lactate is the hallmark of lung injury. The SPA4 peptide on its own and in the presence of lactate exerts anti-inflammatory activity. The primary and secondary structure and the activity of the SPA4 peptide remain intact when pre-incubated in 2 mM sodium lactate solution. The results provide important insights about the stability and structure–activity relationship of the SPA4 peptide. The Royal Society of Chemistry 2023-06-21 /pmc/articles/PMC10282593/ /pubmed/37350860 http://dx.doi.org/10.1039/d3ra02918b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Chowdhury, Asif Alam
Rodgers, Karla
Godbole, Nachiket M.
Awasthi, Shanjana
Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title_full Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title_fullStr Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title_full_unstemmed Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title_short Stability and structure–activity relationship of the SPA4 peptide under ambient and stressed conditions of lung injury
title_sort stability and structure–activity relationship of the spa4 peptide under ambient and stressed conditions of lung injury
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10282593/
https://www.ncbi.nlm.nih.gov/pubmed/37350860
http://dx.doi.org/10.1039/d3ra02918b
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