Figure 8. Trp-Cys contact quenching indicates that in the presence of nortriptyline, the α-syn chain is less compact, more labile and less prone to forming oligomers.

a) Schematic for the determination of the rate of contact formation between the probe, tryptophan (W), and the quencher, cysteine (C), within an unfolded protein. Pulsed optical excitation leads to population of the lowest excited triplet state of tryptophan. Tryptophan contacts cysteine in a diffusion-limited process with rate k_D+, and then either diffuses away (k_D−) or is quenched (q) by the cysteine. b) Reaction-limited and diffusion-limited rates for α-syn without (black) and with (gray) equimolar NOR at 30°C. c) Intramolecular diffusion coefficients calculated at 30°C with the same colors as (b). d) Calculated formation of O (α-syn oligomers), from scheme “i” in the text, for rates describing the protein without (black) and with NOR (gray).