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Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C- or N-terminal lysine side-chain.

ABSTRACT: The attachment of lipids to C- or N-terminally positioned lysine side-chain amino groups increases the activity of a short synthetic (Arg-Trp)3 antimicrobial peptide significantly, making these peptides even active against pathogenic Gram-negative bacteria. Thus, a peptide with strong activity against S. aureus (1.1-2 ?M) and good activity against A. baumannii and P. aeruginosa (9-18 ?M) was identified. The most promising peptide causes 50% hemolysis at 285 ?M and shows some selectivity against human cancer cell lines. Interestingly, the increased activity of ferrocenoylated peptides is mostly due to the lipophilicity of the organometallic fragment.

SUBMITTER: Albada HB

PROVIDER: S-EPMC4025664 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C- or N-terminal lysine side-chain.

Albada H Bauke HB Prochnow Pascal P Bobersky Sandra S Langklotz Sina S Schriek Patrick P Bandow Julia E JE Metzler-Nolte Nils N

ACS medicinal chemistry letters 20120904 12

The attachment of lipids to C- or N-terminally positioned lysine side-chain amino groups increases the activity of a short synthetic (Arg-Trp)3 antimicrobial peptide significantly, making these peptides even active against pathogenic Gram-negative bacteria. Thus, a peptide with strong activity against S. aureus (1.1-2 μM) and good activity against A. baumannii and P. aeruginosa (9-18 μM) was identified. The most promising peptide causes 50% hemolysis at 285 μM and shows some selectivity against ...[more]

PMID: 24900420

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