Extended Data Fig. 7: Additional inhibitors designed for hIAPP fibrils.
From: Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils
a, Proposed model of designed inhibitors (magenta) bound to hIAPP fibrils (blue and grey for each protofilament). The methyl group of N-methylated inhibitors is shown as a green sphere. The last three residues of N4Gm-A are d-amino acids and are underlined. b, ThT assays measuring inhibitor efficacy shown on the left. A9G-A delays hIAPP fibril formation but not N9S-B and N4Gm-A. For the two inhibitors that were not effective, two effective inhibitors (N9S-A and N4Gm-B, respectively) are tested in the same experiment as controls. Data are shown as mean ± s.d., n = 3 independent experiments. c, Negative stain EM images of hIAPP with N9S-A, A9G-A or A9G-B after 20 hours of incubation. Notice that hIAPP fibril formation is not fully eliminated by these inhibitors. d, Negative stain EM shows hIAPP S20G fibrils present after 3 days of incubation with N4Gm-B, suggesting that fibril formation of hIAPP S20G is not fully eliminated when longer incubation times are examined (compared to 20 hours shown in Fig. 3e). Data for graphs in b are available as source data.
