Development of proteolytically stable N-methylated peptide inhibitors of aggregation of the amylin peptide implicated in type 2 diabetes.

ABSTRACT: Islet amyloid polypeptide, also known as amylin, is the main component of the amyloid deposits present in approximately 90% of people with type 2 diabetes mellitus (T2DM). In this disease, amylin aggregates into multimeric β-pleated sheet structures which cause damage to pancreatic islet β-cells. Inhibitors of early-stage amylin aggregation could therefore provide a disease-modifying treatment for T2DM. In this study, overlapping peptides were designed to target the 'binding' region (RLANFLVHSS, residues 11-20) of human amylin, and their effects on amyloid fibril formation were determined by thioflavin-T assay. The first generation peptides showed less than 50% inhibition of aggregation, but a second generation peptide (H₂N-RGANFLVHGR-CONH₂) showed strong inhibitory e

SUBMITTER: Obasse I 

PROVIDER: S-EPMC5665791 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature