Munk, Jens8; Uggerhøj, Lars Erik1; Poulsen, Tanja Juul2; Frimodt-Møller, Niels6; Wimmer, Reinhard1; Nyberg, Nils7; Hansen, Paul Robert7
1 Section of Biotechnology, The Faculty of Engineering and Science, Aalborg University, VBN2 Department of Chemistry and Bioscience, The Faculty of Engineering and Science, Aalborg University, VBN3 The Faculty of Engineering and Science, Aalborg University, VBN4 Microbial Communities, The Faculty of Engineering and Science, Aalborg University, VBN5 University of Copenhagen6 SUND Ph.d. skole7 Natural Products Research8 University of Copenhagen
We present the antimicrobial and hemolytic activities of the decapeptide anoplin and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the effect of altering the charge and hydrophobicity of anoplin on activity against red blood cells and microorganisms. We find that increasing the charge and/or hydrophobicity improves antimicrobial activity and increases hemolytic activity. For each strain tested, we identify at least six anoplin analogs with an improved therapeutic index compared with anoplin, the only exception being Enterococcus faecium, against which only few compounds are more specific than anoplin. Both 2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.
Journal of Peptide Science, 2013, Vol 19, Issue 11, p. 669-675