NDLI: Orientation, Dynamics and Lipid Interaction of an Antimicrobial Arylamide Investigated by 19F and 31P Solid-State NMR Spectroscopy

Content Provider	PubMed Central
Author	Su, Yongchao Degrado, William F. Hong, Mei
Abstract	A number of arylamides have been synthesized and found to exhibit potent antimicrobial activities against a broad spectrum of Gram-positive and Gram-negative bacteria while low toxicity towards eukaryotic cells. These facially amphiphilic foldamers have a relatively rigid intramolecular hydrogen-bonded arylamide as a framework, which places trifluormethyl versus positively charged amino and guanidino groups along opposite faces of the elongated molecule, facilitating interactions with lipid membranes. To better understand the mechanism of action of these antimicrobial foldamers, we have investigated the lipid interaction, depth of insertion, orientation and dynamics of an arylamide, PMX30016, using 31P and 19F solid-state NMR spectroscopy. Static 31P NMR lineshapes of lipid membranes with a range of compositions indicate that PMX30016 does not disrupt the lamellar order of the lipid bilayer, but perturbs the lipid headgroup conformation. This headgroup perturbation, manifested as systematic 31P chemical shift anisotropy increases, is consistent with the well documented “electrometer” effect of lipid membranes in response to the addition of positive charges to membrane surfaces. Paramagnetic relaxation enhancement experiments indicate that the arylamide inserts to the membrane-water interface, just below the headgroup region. Measurement of 19F-19F dipolar couplings within each CF3 moiety revealed that PMX30016 is oriented with the molecular plane 20° and 30° from the membrane normal of neutral and anionic bilayers, respectively, and the long molecular axis lies parallel to the membrane plane. Thus, this arylamide inserts into the bilayer in a knife-like fashion, consistent with previous vibrational spectroscopy results. Moreover, 19F NMR lineshapes indicate that this molecular knife undergoes fast uniaxial rotation around the bilayer normal. These results suggest that antimicrobial arylamides destabilize anionic lipid membranes primarily by altering the membrane electric potential profile, and the spinning molecular knife may additionally create transient defects in the lipid membrane. Compared to typical antimicrobial peptides, this arylamide has more subtle effects on and is less disruptive of the structure of lipid bilayers.
Related Links	http://dx.doi.org/10.1021/ja103658h
Ending Page	9205
Page Count	9
Starting Page	9197
File Format	PDF
ISSN	00027863
e-ISSN	15205126
Journal	Journal of the American Chemical Society
Issue Number	26
Volume Number	132
Language	English
Publisher Date	2010-07-07
Access Restriction	Open
Subject Keyword	Colloid and Surface Chemistry Biochemistry Chemistry(all) Catalysis Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Colloid and Surface Chemistry Biochemistry Catalysis

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