Effects of Disulfide Bond and Cholesterol Derivatives on Human Calcitonin Amyloid Formation

Overview

Journal Biopolymers

Publisher Wiley

Date 2019 Dec 6

PMID 31804717

Citations 2

Authors

Richard Lantz

Brian Busbee

Ewa P Wojcikiewicz

Deguo Du

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Investigating the inhibitory property of DM hCT on hCT fibrillization via its relevant peptide fragments.

Chuang Y, Chang Y, Tu L Protein Sci. 2023; 32(8):e4711.

PMID: 37354016 PMC: 10360389. DOI: 10.1002/pro.4711.

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation.

Lantz R, Busbee B, Wojcikiewicz E, Du D Chemistry. 2020; 26(57):13063-13071.

PMID: 32458489 PMC: 9214666. DOI: 10.1002/chem.202002027.

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