Conformational Exchange on the Microsecond Time Scale in α-Helix and β-Hairpin Peptides Measured by 13C NMR Transverse Relaxation

13C-NMR relaxation experiments (T 1, T 2, T 1 ρ, and NOE) were performed on selectively enriched residues in two peptides, one hydrophobic staple α-helix-forming peptide GFSKAELAKARAAKRGGY and one β-hairpin-forming peptide RGITVNGKTYGR, in water and in water/trifluoroethanol (TFE). Exchange contributions, R ex, to spin−spin relaxation rates for 13Cα and 13Cβ groups were derived and were ascribed to be mainly due to peptide folding−unfolding. To evaluate the exchange time, τex, from R ex, the chemical shift difference between folded and unfolded states, Δδ, and the populations of these states, p i, were determined from the temperature dependence of 13C chemical shifts. For both peptides, values for τex fell in the 1 μs to 10 μs range. Under conditions where the peptides are most folded (water/TFE, 5 °C), τex values for all residues in each respective peptide were essentially the same, supporting the presence of a global folding−unfolding exchange process. Rounded-up average τex values were 4 μs for the helix peptide and 9 μs for the hairpin peptide. This 2−3-fold difference in exchange times between helix and hairpin peptides is consistent with that observed for folding−unfolding of other small peptides.