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Synthesis of imidazolium salt-peptide conjugates and their antimicrobial activity

: Reinhardt, A.; Schmauck, J.; Giernoth, R.; Schubert, A.; Neundorf, I.

Journal of peptide science 20 (2014), No.S1, pp.S259
ISSN: 1075-2617
ISSN: 1099-1387
European Peptide Symposium <33, 2014, Sofia>
Fraunhofer IZI ()

Antimicrobial resistance is still one of the main reasons that lead to prolonged illness, greater risk of death and higher costs. Since new resistance mechanisms steadily emerge there is great demand on new and innovative antibiotics with novel activity spectra [1]. Recently, imidazolium based ionic liquids with antimicrobial activity have been developed by combination of an imidazolium based cation with an anion that has antibiotic activity [2]. In this study two AMPs, sC18[3]and LL-37[4], were covalently coupled to different imidazolium based ionic liquids (IL) in order to increase their antimicrobial effect. Different imidazolium salt-peptide conjugates were generated by solid phase peptide synthesis (SPPS) and tested on Bacillus subtilis, Escherichia coli and Mycobacterium phlei as representatives for gram-positive, gram-negative and acid-fast bacteria. IC50values in the low micro molar range (0.4 -5M) were obtained depending on the imidazolium salt used. Furthermore the conjugates exposed high toxic effects against Vancomycin-Resistant Enterococciand Methicillin-resistant Staphylococcus aureus in a range of 0.3 μM. The tested compounds showed selectivity as they were almost non-toxic against human red blood cells. Selectivity was further studied by experiments using giant unilamellar vesicles that revealed that cholesterol plays a significant role in selectivity. In conclusion, we present here for the first time that the combination of ionic liquid-derived imidazolium salts with antimicrobial peptides leads to highly potent new compounds with promising antibacterial activities.