Conformational Flexibility Of Aggregation-Prone Peptides Studied By Pet-Fcs

Glycine-serine polypeptides in aqueous solution behave as unstructured polymers that exhibit end-to-end contact rates dependent on contour length and in accordance with polymer theory. Aggregation-prone peptides like polyglutamine (poly-Q, associated with various neurodegenerative diseases) of sufficient length were shown to form more collapsed states in aqueous solution. Conformational dynamics mediated by intrachain, interchain, and chain-solvent interactions can reveal mechanistic aspects for the aggregation process that is thought to be responsible for the onset of disease. We used contact-induced fluorescence quenching due to photoinduced electron transfer (PET) between terminally attached oxazine fluorophores and tryptophan for studying peptide loop closure rates on ns-μs time scales. Conformational dynamics as function of temperature, solvent viscosity, and osmolyte concentrations were analyzed using fluorescence correlation spectroscopy (PET-FCS). Significantly smaller end-to-end contact rates for poly-Q and related peptides as compared to poly-GS peptides with a viscosity-dependence hinting at internal friction were found.