Calcitonin is a 32-residue peptide that contains an intrachain disulfide bond, between Cys1 and Cys7, and is secreted by the C-cells of the thyroid to regulate calcium in the body. Amyloid formation of this peptide is associated with medullary carcinoma of the thyroid. The aim of this study is to probe the mechanism of aggregation of human calcitonin, with and without the formation of the disulfide bond, and to investigate small molecule inhibitors of this amyloidogenic peptide. AFM imaging showed that when the disulfide bond is reduced, there was no amyloid fibril formation and only spherical oligomers formed. However, when the cysteine residues were oxidized and established a disulfide bond, short fibrils were seen. These results imply that the disulfide bond is important in the mechanism of calcitonin amyloid formation. Also, a cholesterol derivative (DC-Cholesterol) and baicalein decreased the fluorescence signal in a ThT binding assay. This suggests that these molecules may play a role in regulating calcitonin amyloid formation.<br/>

Investigating calcitonin aggregation through oxidation of the disulfide bond and inhibition with small molecules

2019 Spring National Meeting

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