Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment
Abstract 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 conventiona...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-16303-2 |
| _version_ | 1811293449634185216 |
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| author | Pratibha Sharma Sheetal Sharma Shubhi Joshi Panchali Barman Aashish Bhatt Mayank Maan Neha Singla Praveen Rishi Md. Ehesan Ali Simran Preet Avneet Saini |
| author_facet | Pratibha Sharma Sheetal Sharma Shubhi Joshi Panchali Barman Aashish Bhatt Mayank Maan Neha Singla Praveen Rishi Md. Ehesan Ali Simran Preet Avneet Saini |
| author_sort | Pratibha Sharma |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T05:01:35Z |
| format | Article |
| id | doaj.art-463bea5de87f456db58cc58542246176 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T05:01:35Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-463bea5de87f456db58cc585422461762022-12-22T03:01:18ZengNature PortfolioScientific Reports2045-23222022-07-0112111410.1038/s41598-022-16303-2Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragmentPratibha Sharma0Sheetal Sharma1Shubhi Joshi2Panchali Barman3Aashish Bhatt4Mayank Maan5Neha Singla6Praveen Rishi7Md. Ehesan Ali8Simran Preet9Avneet Saini10Department of Biophysics, Panjab UniversityDepartment of Biophysics, Panjab UniversityEnergy Research Centre, Panjab UniversityInstitute of Forensic Science and Criminology (UIEAST), Panjab UniversityInstitute of Nano Science and TechnologyDepartment of Biophysics, Panjab UniversityDepartment of Biophysics, Panjab UniversityDepartment of Microbiology, Panjab UniversityInstitute of Nano Science and TechnologyDepartment of Biophysics, Panjab UniversityDepartment of Biophysics, Panjab UniversityAbstract 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.https://doi.org/10.1038/s41598-022-16303-2 |
| spellingShingle | Pratibha Sharma Sheetal Sharma Shubhi Joshi Panchali Barman Aashish Bhatt Mayank Maan Neha Singla Praveen Rishi Md. Ehesan Ali Simran Preet Avneet Saini Design, characterization and structure–function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-16303-2 |
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