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An amphipathic cyclic tetrapeptide scaffold containing halogenated β 2,2 ‐amino acids with activity against multiresistant bacteria
Author(s) -
Paulsen Marianne H.,
Karlsen Eskil André,
Ausbacher Dominik,
Anderssen Trude,
Bayer Annette,
Ochtrop Philipp,
Hedberg Christian,
Haug Tor,
Ericson Sollid Johanna U.,
Strøm Morten B.
Publication year - 2018
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3117
Subject(s) - tetrapeptide , antimicrobial , chemistry , residue (chemistry) , peptide , amino acid , bacteria , cyclic peptide , antimicrobial peptides , biological activity , stereochemistry , antibiotics , antibacterial activity , amphiphile , biochemistry , in vitro , biology , organic chemistry , copolymer , genetics , polymer
The present study describes the synthesis and biological studies of a small series of head‐to‐tail cyclic tetrapeptides of the general structure c(Lys‐β 2,2 ‐Xaa‐Lys) containing one lipophilic β 2,2 ‐amino acid and Lys, Gly, Ala, or Phe as the Xaa residue in the sequence. The peptides were investigated for antimicrobial activity against gram‐positive and gram‐negative reference strains and 30 multiresistant clinical isolates including strains with extended spectrum β‐lactamase—carbapenemase (ESBL‐CARBA) production. Toxicity was determined against human red blood cells. The most potent peptides showed high activity against the gram‐positive clinical isolates with minimum inhibitory concentrations of 4–8 μg/mL and low haemolytic activity. The combination of high antimicrobial activity and low toxicity shows that these cyclic tetrapeptides containing lipophilic β 2,2 ‐amino acids form a valuable scaffold for designing novel antimicrobial agents.