Effects of disulfide bond and cholesterol derivatives on human calcitonin amyloid formation

Lantz, Richard; Busbee, Brian; Wojcikiewicz, Ewa P.; Du, Deguo

doi:10.1002/bip.23343

Cited by 7 publications

(8 citation statements)

References 61 publications

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“…ThT selectively binds to the amyloid fibrillar structure, leading to an increase in the fluorescence intensity in the vicinity of 480 nm . As shown in Figure B, the aggregation kinetics of hCT shows a fast increase in fluorescence intensity until it reaches maximum intensity at ≈9 h. This result is in accordance with previous reports indicating rapid hCT amyloid formation . Notably, after reaching the maximum, the fluorescence intensity slowly declines over time.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, after reaching the maximum, the fluorescence intensity slowly declines over time. This is consistent with other reports where the decrease of the signal is likely attributed to the precipitation of hCT aggregates over the incubation period . When 5 μ m EGCG is added, there is a ≈50 % decrease in the maximum ThT fluorescence intensity compared to that of hCT only (Figure B).…”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with other reports where the decrease of the signali s likely attributed to the precipitation of hCT aggregates over the incubation period. [36][37] When 5 mm EGCG is added, there is a % 50 %d ecreasei nt he maximum ThT fluorescencei ntensity compared to that of hCT only ( Figure 1B). In the presence of 50 mm EGCG,t he maximum fluorescencei ntensity is reduced by % 80 %.…”

Section: Inhibitory Effect Of Egcg Analogues On Hct Amyloidogenesismentioning

confidence: 97%

“…[32][33][34] As shown in Figure 1B,t he aggregation kinetics of hCT shows af ast increase in fluorescence intensity until it reachesm aximum intensity at % 9h.T his result is in accordancew ith previous reports indicating rapid hCT amyloid formation. [6,[35][36] Notably,a fter reaching the maximum, the fluorescencei ntensity slowly declines over time. This is consistent with other reports where the decrease of the signali s likely attributed to the precipitation of hCT aggregates over the incubation period.…”

Section: Inhibitory Effect Of Egcg Analogues On Hct Amyloidogenesismentioning

confidence: 99%

“…The molecular weight of the peptide was confirmed with matrix-assisted laser desorption ionization (MALDI) mass spectrometry.A ir oxidation was used to form the hCT disulfide bond as previously described. [36] Briefly,h CT was dissolved under dilute conditions in 6 m urea (pH 8.1) to prevent fibrillization. [19,85] The solution was incubated overnight with air bubbling to form the disulfide bond between Cys1 and Cys7.…”

Section: Synthesis and Preparation Of Hctmentioning

confidence: 99%

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Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Lantz

Busbee

Wojcikiewicz

et al. 2020

Chemistry A European J

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Humanc alcitonin (hCT) is a3 2-residue peptide hormone that can aggregate into amyloid fibrils and cause cellulart oxicity.I nt his study,w ei nvestigated the inhibition effects of ag roup of polyphenolic molecules on hCT amyloid formation. Our results suggest that the gallate moiety in epigallocatechin-3-gallate (EGCG), aw ell-recognized amyloid inhibitor,i sn ot criticalf or its inhibition function in the hCT amyloid formation. Ourr esults demonstrate that flavonoid compounds, such as myricetin, quercetin, and baicalein, that containv icinal hydroxyl groupso nt he phenyl ring effectively prevent hCT fibrillization. This structural feature may also be appliedt on on-flavonoidp olyphenolici nhibitors.M ore-over,o ur results indicate ap lausible mechanistic role of these vicinal hydroxylg roups which might include the oxidationto form aq uinone and the subsequent covalentl inkage with amino acid residuess uch as lysineo rh istidine in hCT.T his may furtherd isrupt the crucial electrostatic and aromatic interactions involved in the process of hCT amyloid fibril formation. The inhibition activity of the polyphenolic compounds against hCT fibril formationm ay likely be attributed to ac ombinationo ff actorss uch as covalentl inkage formation,aromatic stacking,a nd hydrogen bonding interactions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Inhibitory Effect Of Egcg Analogues On Hct Amyloidogenesismentioning

confidence: 97%

Section: Inhibitory Effect Of Egcg Analogues On Hct Amyloidogenesismentioning

confidence: 99%

Section: Synthesis and Preparation Of Hctmentioning

confidence: 99%

See 3 more Smart Citations

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Lantz

Busbee

Wojcikiewicz

et al. 2020

Chemistry A European J

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

Chuang

Chang

2023

Protein Science

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The irreversible aggregation of proteins or peptides greatly limits their bioavailability; therefore, effective inhibition using small molecules or biocompatible materials is very difficult. Human calcitonin (hCT), a hormone polypeptide with 32 residues, is secreted by the C-cells of the thyroid gland.The biological function of this hormone is to regulate calcium and phosphate concentrations in the blood via several different pathways. One of these is to inhibit the activity of osteoclasts; thus, calcitonin could be used to treat osteoporosis and Paget's disease of the bone. However, hCT is prone to aggregation in aqueous solution and forms amyloid fibrils. Salmon and eel calcitonin are currently used as clinical substitutes for hCT. In a previous study, we found that the replacement of two residues at positions 12 and 17 of hCT with amino acids that appear in the salmon sequence can greatly suppress peptide aggregation. The double mutations of hCT (DM hCT) also act as good inhibitors by disrupting wild-type hCT fibrillization, although the inhibition mechanism is not clear. More importantly, we demonstrated that DM hCT is biologically active in interacting with the calcitonin receptor. To further understand the

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Expanding peptide-cucurbit[7]uril interactions through selective N-terminal reductive alkylation

Meudom

Zheng

Zhu

et al. 2022

Current Research in Chemical Biology

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Effects of disulfide bond and cholesterol derivatives on human calcitonin amyloid formation

Cited by 7 publications

References 61 publications

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

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

Expanding peptide-cucurbit[7]uril interactions through selective N-terminal reductive alkylation

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