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. Author manuscript; available in PMC: 2017 Aug 24.
Published in final edited form as: Chem Rev. 2017 Jan 6;117(16):10726–10759. doi: 10.1021/acs.chemrev.6b00582

Figure 24.

Figure 24

Rapid-scan 2D IR reveals a transient β-sheet intermediate during hIAPP aggregation. The FGAIL segment (residues 23–27) is shown in red. Macrocyclic inhibitors (Mac21–27) can bind to and stabilize the intermediate FGAIL β-sheet (cyan), thus increasing the free energy barrier. Some macrocycles seed fibril growth and circumvent the barrier (green arrow). Aggregation is inhibited by mutations such as I26P, which destabilize the intermediate (dashed black line). The addition of Mac21–27 can induce formation of the transient intermediate even for the mutated sequence (dashed cyan line). Reproduced with permission from ref 26. Copyright 2013 National Academy of Sciences.