A hIAPP-derived all-D-amino-acid inhibits hIAPP fibrillation efficiently at membrane surface by targeting α-helical oligomeric intermediates.

A variety of peptides and peptide derivatives have been constructed using the "β-sheet core segment" of amyloid proteins as inhibitors of amyloidogenic fibrillation. A novel all-D-amino-acid from hIAPP β-sheet core segment (hIAPP 22-27) is demonstrated to inhibit hIAPP fibril formation efficiently both at the phospholipid membrane and in bulk solution. The inhibitor terminates hIAPP aggregation to the α-helical oligomeric intermediates at the membrane surface, whereas it stops the aggregation at the stage of β-sheet oligomeric intermediates in bulk solution. This is the first evidence that the inhibition mechanism of the inhibitor at membrane surface is significantly different from that in bulk solution.