Uggerhøj, Lars Erik2; Munk, Jens K.3; Hansen, Paul Robert5; Güntert, Peter3; Wimmer, Reinhard2
1 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet2 Sektion for Bioteknologi3 unknown4 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet5 Department of Drug Design and Pharmacology, Faculty of Pharmaceutical Sciences, Københavns Universitet
The inclusion of peptoid monomers into antimicrobial peptides (AMPs) increases their proteolytic resistance, but introduces conformational flexibility (reduced hydrogen bonding ability and cis/trans isomerism). We here use NMR spectroscopy to answer how the insertion of a peptoid monomer influences the structure of a regular α-helical AMP upon interaction with a dodecyl phosphocholine (DPC) micelle. Insertion of [(2-methylpropyl)amino]acetic acid in maculatin-G15 shows that the structural change and conformational flexibility depends on the site of insertion. This is governed by the micelle interaction of the amphipathic helices flanking the peptoid monomer and the side chain properties of the peptoid and its preceding residue.
F E B S Letters, 2014, Vol 588, Issue 17, p. 3291-3297