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Publication Abstract from PubMed

Antimicrobial peptides (AMPs) are promising candidates for battling multiresistant bacteria. Despite extensive research, structure-activity relationships of AMPs are not fully understood, and there is a lack of structural data relating to AMPs in lipids. Here we present the NMR structure of anoplin (GLLKRIKTLL-NH2 ) in a micellar environment. A vast library of substitutions was designed and tested for antimicrobial and hemolytic activity, as well as for changes in structure and lipid interactions. This showed that improvement of antimicrobial activity without concomitant introduction of strong hemolytic activity can be achieved through subtle increases in the hydrophobicity of the hydrophobic face or through subtle increases in the polarity of the hydrophilic face of the helix, or-most efficiently-a combination of both. A set of guidelines based on the results is given, for assistance in how to modify cationic alpha-helical AMPs in order to control activity and selectivity. The guidelines are finally tested on a different peptide.

Rational Design of Alpha-Helical Antimicrobial Peptides: Do's and Don'ts.,Uggerhoj LE, Poulsen TJ, Munk JK, Fredborg M, Sondergaard TE, Frimodt-Moller N, Hansen PR, Wimmer R Chembiochem. 2015 Jan 19;16(2):242-53. doi: 10.1002/cbic.201402581. Epub 2014 Dec, 21. PMID:25530580^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.