Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities

Abstract Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We ha...

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Autores principales:	Amit Kumar Tripathi, Tripti Kumari, Munesh Kumar Harioudh, Pranjal Kumar Yadav, Manoj Kathuria, P. K. Shukla, Kalyan Mitra, Jimut Kanti Ghosh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e1c123319824999a8c40701518f5bf8
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spelling	oai:doaj.org-article:8e1c123319824999a8c40701518f5bf82021-12-02T12:31:53ZIdentification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities10.1038/s41598-017-03576-12045-2322https://doaj.org/article/8e1c123319824999a8c40701518f5bf82017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03576-1https://doaj.org/toc/2045-2322Abstract Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells. Further, these analogs showed broad-spectrum activity against Gram-positive, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus strains and fungi and also retained antibacterial activity in presence of physiological salts, serum and at elevated temperatures indicative of their therapeutic potential. These Chrysophsin-1 analogs also inhibited lipopolysaccharide (LPS) induced pro-inflammatory responses in THP-1 cells and in murine primary macrophages. One of these single proline-substituted Chrysophsin-1 analogs inhibited LPS-stimulated pro-inflammatory cytokine production in BALB/c mice and elicited appreciable survival of mice administered with a lethal dose of LPS in a model of severe sepsis. The data for the first time showed the implication of GXXXXG motifs in functional and biological properties of an antimicrobial peptide and could be useful to design novel anti-microbial and anti-endotoxin peptides by employing this motif.Amit Kumar TripathiTripti KumariMunesh Kumar HarioudhPranjal Kumar YadavManoj KathuriaP. K. ShuklaKalyan MitraJimut Kanti GhoshNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amit Kumar Tripathi Tripti Kumari Munesh Kumar Harioudh Pranjal Kumar Yadav Manoj Kathuria P. K. Shukla Kalyan Mitra Jimut Kanti Ghosh Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
description	Abstract Marine fish antimicrobial peptide, chrysophsin-1 possesses versatile biological activities but its non-selective nature restricts its therapeutic possibilities. Often small alterations in structural motifs result in significant changes in the properties of concerned proteins/peptides. We have identified GXXXXG motif in chrysophsin-1. Glycine residue(s) of this motif in Chrysophsin-1 was/were replaced with alanine, valine and proline residue(s). Of these, proline-substituted Chrysophsin-1 analogs exhibited significantly reduced cytotoxicity towards mammalian cells. Further, these analogs showed broad-spectrum activity against Gram-positive, Gram-negative bacteria, Methicillin-resistant Staphylococcus aureus strains and fungi and also retained antibacterial activity in presence of physiological salts, serum and at elevated temperatures indicative of their therapeutic potential. These Chrysophsin-1 analogs also inhibited lipopolysaccharide (LPS) induced pro-inflammatory responses in THP-1 cells and in murine primary macrophages. One of these single proline-substituted Chrysophsin-1 analogs inhibited LPS-stimulated pro-inflammatory cytokine production in BALB/c mice and elicited appreciable survival of mice administered with a lethal dose of LPS in a model of severe sepsis. The data for the first time showed the implication of GXXXXG motifs in functional and biological properties of an antimicrobial peptide and could be useful to design novel anti-microbial and anti-endotoxin peptides by employing this motif.
format	article
author	Amit Kumar Tripathi Tripti Kumari Munesh Kumar Harioudh Pranjal Kumar Yadav Manoj Kathuria P. K. Shukla Kalyan Mitra Jimut Kanti Ghosh
author_facet	Amit Kumar Tripathi Tripti Kumari Munesh Kumar Harioudh Pranjal Kumar Yadav Manoj Kathuria P. K. Shukla Kalyan Mitra Jimut Kanti Ghosh
author_sort	Amit Kumar Tripathi
title	Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
title_short	Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
title_full	Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
title_fullStr	Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
title_full_unstemmed	Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
title_sort	identification of gxxxxg motif in chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8e1c123319824999a8c40701518f5bf8
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Identification of GXXXXG motif in Chrysophsin-1 and its implication in the design of analogs with cell-selective antimicrobial and anti-endotoxin activities

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