Fibrillation of Human Calcitonin and Its Analogs: Effects of Phosphorylation and Disulfide Reduction.

ABSTRACT: Some therapeutic peptides self-assemble in solution to form ordered, insoluble, β-sheet-rich amyloid fibrils. This physical instability can result in reduced potency, cause immunogenic side effects, and limit options for formulation. Understanding the mechanisms of fibrillation is key to developing rational mitigation strategies. Here, amide hydrogen-deuterium exchange with mass spectrometric analysis (HDX-MS) coupled with proteolytic digestion was used to identify the early stage interactions leading to fibrillation of human calcitonin (hCT), a peptide hormone important in calcium metabolism. hCT fibrillation kinetics was sigmoidal, with lag, growth, and plateau phases as shown by thioflavin T and turbidity measurements. HDX-MS of fibrillating hCT (pH 7.4; 25°C) suggested early involvemen

SUBMITTER: Renawala HK 

PROVIDER: S-EPMC7820727 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature