title: A hIAPP-derived all-D-amino-acid inhibits hIAPP fibrillation efficiently at membrane surface by targeting α-helical oligomeric intermediates.
abstract: 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.
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Life Science, Jilin University, Changchun 130012, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, PR China. Electronic address: feili@jlu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000686:Amyloidosis / Q000188:drug therapy; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D051381:Rats; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D009842:Oligopeptides; D053835:Unilamellar Liposomes; C478380:amylin (22-27)
keywords: All-d-amino-acid inhibitor; Fibrillogenesis; Phospholipid membrane; hIAPP; α-Helical intermediate