| Autor: |
Ida Kristine Lysgaard Andersen, Thomas T. Thomsen, Jasmina Rashid, Thomas Rønnemoes Bobak, Alberto Oddo, Henrik Franzyk, Anders Løbner-Olesen, Paul R. Hansen |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Antibiotics, Vol 11, Iss 8, p 1080 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2079-6382 |
| DOI: |
10.3390/antibiotics11081080 |
| Popis: |
BP214 is an all-D antimicrobial peptide amide, kklfkkilryl, which shows an excellent activity against colistin-resistant Acinetobacter baumannii and a low hemolytic activity. The aim of the present work was to investigate how C-terminus-to-side chain macrocyclization and fatty acid modification affect the antimicrobial and hemolytic activity of this peptide. In total, 18 analogs of BP214 were synthesized using a combination of Fmoc-based solid-phase peptide synthesis and the submonomer approach. Cyclization was achieved by reacting the ε-amino group of a C-terminal lysine residue with a bromoacetylgroup attached to the Nα amino group of the N-terminal amino acid, generating a secondary amine at which the exocyclic lipopeptide tail was assembled. Three different ring sizes (i.e., 3–5 amino acid residues) of C-locked analogs combined with fatty acids of different lengths (i.e., C10–C14) were investigated. The antimicrobial activity of the analogs was tested against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The most promising compound was analog 13 (MIC = 4 µg/mL (2.4 µM) against E. coli and 36% hemolysis of red blood cells at 150 µM). In a time-kill assay, this peptide showed a significant, concentration-dependent reduction in viable E. coli cells comparable to that seen for colistin. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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