Design, characterization and structure-function analysis of novel antimicrobial peptides based on the N-terminal CATH-2 fragment.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 07 2022
14 07 2022
Historique:
received:
13
04
2022
accepted:
07
07
2022
entrez:
14
7
2022
pubmed:
15
7
2022
medline:
19
7
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35835842
doi: 10.1038/s41598-022-16303-2
pii: 10.1038/s41598-022-16303-2
pmc: PMC9283491
doi:
Substances chimiques
Anti-Bacterial Agents
0
Anti-Infective Agents
0
Antimicrobial Cationic Peptides
0
Antimicrobial Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12058Informations de copyright
© 2022. The Author(s).
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