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Effects of disulfide bond and cholesterol derivatives on human calcitonin amyloid formation
Author(s) -
Lantz Richard,
Busbee Brian,
Wojcikiewicz Ewa P.,
Du Deguo
Publication year - 2020
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23343
Subject(s) - chemistry , cholesterol , intramolecular force , amyloid (mycology) , vesicle , disulfide bond , fibril , kinetics , peptide , hydrogen bond , biophysics , biochemistry , stereochemistry , molecule , organic chemistry , membrane , inorganic chemistry , physics , quantum mechanics , biology
Human calcitonin (hCT) is a 32‐residue peptide that aggregates to form amyloid fibrils under appropriate conditions. In this study, we investigated the effect of the intramolecular disulfide bond formed at the N‐terminal region of the peptide in the aggregation kinetics of hCT. Our results indicate that the presence of the disulfide bond in hCT plays a crucial role in forming the critical nucleus needed for fibril formation, facilitating the rate of hCT amyloidogenesis. Furthermore, we reported for the first time the effects of cholesterol, cholesterol sulfate, and 3β‐[N‐(dimethylaminoethane)carbamoyl]‐cholesterol (DC‐cholesterol) on the amyloid formation of oxidized hCT. Our results show that while cholesterol does not affect amyloidogenesis of oxidized hCT, high concentrations of cholesterol sulfate exhibits a moderate inhibiting activity on hCT amyloid formation. In particular, our results show that DC‐cholesterol strongly inhibits amyloidogenesis of oxidized hCT in a dose‐dependent manner. Further studies at different pH conditions imply the crucial impact of electrostatic and hydrogen bonding interactions in mediating the interplay of hCT and the surface of DC‐cholesterol vesicles and the inhibiting function of DC‐cholesterol on hCT fibrillization.