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Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment
The emergence of multidrug resistance coupled with shrinking antibiotic pipelines has increased the demand of antimicrobials with novel mechanisms of action. Therefore, researchers across the globe are striving to develop new antimicrobial substances to alleviate the pressure on conventional antibio...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283491/ https://www.ncbi.nlm.nih.gov/pubmed/35835842 http://dx.doi.org/10.1038/s41598-022-16303-2 |
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author | Sharma, Pratibha Sharma, Sheetal Joshi, Shubhi Barman, Panchali Bhatt, Aashish Maan, Mayank Singla, Neha Rishi, Praveen Ali, Md. Ehesan Preet, Simran Saini, Avneet |
author_facet | Sharma, Pratibha Sharma, Sheetal Joshi, Shubhi Barman, Panchali Bhatt, Aashish Maan, Mayank Singla, Neha Rishi, Praveen Ali, Md. Ehesan Preet, Simran Saini, Avneet |
author_sort | Sharma, Pratibha |
collection | PubMed |
description | The emergence of multidrug resistance coupled with shrinking antibiotic pipelines has increased the demand of antimicrobials with novel mechanisms of action. Therefore, researchers across the globe are striving to develop new antimicrobial substances to alleviate the pressure on conventional antibiotic therapies. Host-Defence Peptides (HDPs) and their derivatives are emerging as effective therapeutic agents against microbial resistance. In this study, five analogs (DP1-5) of the N-terminal (N-15) fragment of CATH-2 were designed based on the delicate balance between various physicochemical properties such as charge, aliphatic character, amphipathicity and hydrophobicity. By means of in-silico and in-vitro studies a novel peptide (DP1) with the sequence “RFGRFLRKILRFLKK” was found to be more effective and less toxic than the N-terminal CATH-2 peptide. Circular dichroism spectroscopy and differential scanning calorimetry were applied for structural insights. Antimicrobial, haemolytic, and cytotoxic activities were also assessed. The resulting peptide was characterized by low cytotoxicity, low haemolytic activity, and efficient anti-microbial activity. Structurally, it displayed strong helical properties irrespective of the solvent environment and was stable in membrane-mimicking environments. Taken together, the data suggests that DP1 can be explored as a promising therapeutic agent with possible clinical applications. |
format | Online Article Text |
id | pubmed-9283491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92834912022-07-16 Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment Sharma, Pratibha Sharma, Sheetal Joshi, Shubhi Barman, Panchali Bhatt, Aashish Maan, Mayank Singla, Neha Rishi, Praveen Ali, Md. Ehesan Preet, Simran Saini, Avneet Sci Rep Article The emergence of multidrug resistance coupled with shrinking antibiotic pipelines has increased the demand of antimicrobials with novel mechanisms of action. Therefore, researchers across the globe are striving to develop new antimicrobial substances to alleviate the pressure on conventional antibiotic therapies. Host-Defence Peptides (HDPs) and their derivatives are emerging as effective therapeutic agents against microbial resistance. In this study, five analogs (DP1-5) of the N-terminal (N-15) fragment of CATH-2 were designed based on the delicate balance between various physicochemical properties such as charge, aliphatic character, amphipathicity and hydrophobicity. By means of in-silico and in-vitro studies a novel peptide (DP1) with the sequence “RFGRFLRKILRFLKK” was found to be more effective and less toxic than the N-terminal CATH-2 peptide. Circular dichroism spectroscopy and differential scanning calorimetry were applied for structural insights. Antimicrobial, haemolytic, and cytotoxic activities were also assessed. The resulting peptide was characterized by low cytotoxicity, low haemolytic activity, and efficient anti-microbial activity. Structurally, it displayed strong helical properties irrespective of the solvent environment and was stable in membrane-mimicking environments. Taken together, the data suggests that DP1 can be explored as a promising therapeutic agent with possible clinical applications. Nature Publishing Group UK 2022-07-14 /pmc/articles/PMC9283491/ /pubmed/35835842 http://dx.doi.org/10.1038/s41598-022-16303-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sharma, Pratibha Sharma, Sheetal Joshi, Shubhi Barman, Panchali Bhatt, Aashish Maan, Mayank Singla, Neha Rishi, Praveen Ali, Md. Ehesan Preet, Simran Saini, Avneet Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title | Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title_full | Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title_fullStr | Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title_full_unstemmed | Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title_short | Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment |
title_sort | design, characterization and structure–function analysis of novel antimicrobial peptides based on the n-terminal cath-2 fragment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283491/ https://www.ncbi.nlm.nih.gov/pubmed/35835842 http://dx.doi.org/10.1038/s41598-022-16303-2 |
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