Probing the Micelle‐Bound Aggregation‐Prone State of α‐Synuclein with ¹⁹F NMR Spectroscopy

19F NMR as a tool in chemical biology

“…19 F NMR has also been applied to study the conformational heterogeneity and dynamics of a broad range of proteins and peptides upon their interaction with model lipid vesicles [ 59 ], micelles [ 60 ] and bicelles [ 61 ]. It has enabled the quantification and mechanistic characterization of intermolecular dynamic processes such as protein dimerization, oligomerization and fibrillation, even within large and especially complex systems [ 62 – 63 ].…”

“…Also shown are the 19 F NMR spectra of the corresponding 4-tfmF-labelled peptides at positions 4, 39, 70 and 133 in varying concentrations of SDS. Figure 11 is reproduced from [ 60 ]. Copyright © 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…Overall, the work showed the potential applicability of 19 F NMR PREs as excellent alternative parameters for the quantitative analysis of site-specific intramolecular distances, with a more particular significant value in the exploration of large proteins and macromolecular complexes where substrate spectral crowding and/or background incompatibility prevents the use of other nuclei such as 1 H or 15 N PREs. 19 F NMR has also been applied to study the conformational heterogeneity and dynamics of a broad range of proteins and peptides upon their interaction with model lipid vesicles [59], micelles [60] and bicelles [61]. It has enabled the quantification and mechanistic characterization of intermolecular dynamic processes such as protein dimerization, oligomerization and fibrillation, even within large and especially complex systems [62,63].…”

“…In this work 19 F NMR was employed to study several properties of a specifically 3-FTyr-labelled α-synuclein analogue, including its native conformation and the conformational changes induced by urea, spermine and sodium dodecyl sulfate (SDS) [75]. Subsequently, α-synuclein interaction with SDS micelles and model membranes have also been investigated in detail [59,76], as well as the kinetics of α-Syn oligomerization and fibril formation both in vitro [60,75] and in vivo [77,78]. In these more recent studies, incorporation of 4-tfmF residues using amber-suppressing codons at various positions was shown to be more advantageous as a 19 F reporting strategy, owing to the higher sensitivity and improved NMR relaxation properties of the CF 3 -group.…”

Fluorinated amino acids in amyloid formation: a symphony of size, hydrophobicity and α-helix propensity

“…[30][31][32][33][34][35] A common application is the use of uorinated amino acids as NMR-labels to gain insight into the mechanism of structural conversion and amyloid formation. 8,[36][37][38] The Ramamoorthy and Marsh groups have used uorinated amino acids as NMR-labels to follow the aggregation pathway of IAPP and Ab. 39,40 Senguen and co-workers used highly uorinated Phe to evaluate its aromatic, hydrophobic and steric effects on the self-assembly of the amyloid-b-fragment Ab (16)(17)(18)(19)(20)(21)(22).…”