Using a Sterically Restrictive Amino Acid as a 19F NMR label To Monitor and To Control Peptide Aggregation in Membranes

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• 作者：Parvesh Wadhwani ; Jochen Bü ; rck ; Erik Strandberg ; Christian Mink ; Sergii Afonin ; Anne S. Ulrich
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：December 10, 2008
• 年：2008
• 卷：130
• 期：49
• 页码：16515-16517
• 全文大小：233K
• 年卷期：v.130,no.49(December 10, 2008)
• ISSN：1520-5126

文摘

Aggregation of peptides into amyloid fibrils or other β-sheet structures is usually related to malfunction. This process is often induced by lipid bilayers but is difficult to monitor in the membrane-bound state. Here, we show how aggregation is readily detected by solid state ¹⁹F NMR using a fluorine-labeled amino acid and how the same sterically rigid side chain can be also be employed to prevent aggregation. Selective CF₃-phenylglycine labels were incorporated either as the L- or D-enantiomer into the membrane-active model amphiphilic peptide (MAP). Oriented circular dichroism showed that the D-epimeric peptides maintained an α-helical conformation in DMPC at all peptide-to-lipid ratios, while the L-epimers turned into β-sheet structures above 1:200, just like the wild-type. Aggregation was clearly revealed by the appearance of powder lineshapes in the ¹⁹F NMR spectra of oriented samples. The ¹⁹F NMR dipolar couplings from four D-epimers were analyzed as orientational constraints, showing that the helix of MAP undergoes a concentration-dependent realignment in DMPC from a surface-bound to a tilted state.