C-locked analogs of the antimicrobial peptide BP214
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C-locked analogs of the antimicrobial peptide BP214. / Andersen, Ida Kristine Lysgaard; Thomsen, Thomas Thyge; Rashid, Jasmina; Bobak, Thomas Rønnemoes; Oddo, Alberto; Franzyk, Henrik; Løbner-Olesen, Anders; Hansen, Paul Robert.
In: Antibiotics, Vol. 11, No. 8, 1080, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - C-locked analogs of the antimicrobial peptide BP214
AU - Andersen, Ida Kristine Lysgaard
AU - Thomsen, Thomas Thyge
AU - Rashid, Jasmina
AU - Bobak, Thomas Rønnemoes
AU - Oddo, Alberto
AU - Franzyk, Henrik
AU - Løbner-Olesen, Anders
AU - Hansen, Paul Robert
N1 - This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.3390/antibiotics11081080
DO - 10.3390/antibiotics11081080
M3 - Journal article
C2 - 36009951
VL - 11
JO - Antibiotics
JF - Antibiotics
SN - 2079-6382
IS - 8
M1 - 1080
ER -
ID: 312112456