Munk, Jens8; Uggerhøj, Lars Erik3; Poulsen, Tanja Juul4; Frimodt-Møller, Niels5; Wimmer, Reinhard4; Nyberg, Niels T.6; Hansen, Paul Robert9
1 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet2 Chemistry and Biochemistry, Department of Basic Sciences and Environment, Faculty of Life Sciences, Københavns Universitet3 Sektion for Bioteknologi4 Institut for Kemi og Bioteknologi5 Hvidovre Hospital6 Katholieke Universiteit7 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet8 Chemistry and Biochemistry, Department of Basic Sciences and Environment, Faculty of Life Sciences, Københavns Universitet9 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet
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. 669-75