2D-IR spectra and kinetics curves of human IAPP with 13C=18O labeled at the Ala25 residue [113]. (A) The first 2D-IR spectrum at t = 5 min. (B–D) Difference 2D-IR spectra at t = 31, 66, and 205 min, calculated by subtracting the t = 5 min spectrum. Black boxes surround the spectral features of the unlabeled portion of the peptide, whereas red boxes enclose the diagonal peaks of the isotope labeled Ala25. Blue and green arrows highlight the 2 labeled features, whereas magenta and red arrows point to the cross-peak between the 13C=18O Ala25 and the unlabeled β-sheet. (E) Kinetics of the diagonal peaks of the unlabeled β-sheet at 1617 cm−1 and the 2 label features (blue and green arrows). (F) Comparison of the kinetics of the cross-peak and the diagonal peaks. Reprinted with permission.