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
Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
Hospital Pharmacy of North Norway Trust, Tromsø, Norway.
J Pept Sci. 2018 Oct;24(10):e3117. doi: 10.1002/psc.3117. Epub 2018 Aug 15.
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 -Xaa-Lys) containing one lipophilic β -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 -amino acids form a valuable scaffold for designing novel antimicrobial agents.
本研究描述了一系列具有通式c（Lys-β-Xaa-Lys）的头对尾环四肽的合成及生物学研究，该系列环四肽含有一个亲脂性β-氨基酸，且序列中的Xaa残基为Lys、Gly、Ala或Phe。研究了这些肽对革兰氏阳性和革兰氏阴性参考菌株以及30株多重耐药临床分离株（包括产超广谱β-内酰胺酶-碳青霉烯酶（ESBL-CARBA）的菌株）的抗菌活性。测定了其对人红细胞的毒性。最有效的肽对革兰氏阳性临床分离株表现出高活性，最低抑菌浓度为4-8μg/mL，且溶血活性低。高抗菌活性和低毒性的结合表明，这些含有亲脂性β-氨基酸的环四肽构成了设计新型抗菌剂的有价值支架。
