The inhibitory effect and mechanism of small molecules on acetic anhydride-induced BSA acetylation and aggregation

Huo, Xingli; Liu, Huijun; Wang, Shengjie; Yin, Shanmei; Yin, Zongning

doi:10.1016/j.colsurfb.2023.113265

Cited by 5 publications

(1 citation statement)

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“…In early stages of the drug-discovery process in neurodegenerative diseases, often modulators of amyloid aggregation are screened employing protein/peptide amyloids which, even not strictly involved in neurodegeneration, are assumed as structural models of amyloids. − In this context, nucleophosmin 1 (NPM1) is not a neurodegenerative protein but contains, in the second helix of its C-terminal domain, a well-characterized fragment, 264–277 peptide, able to act as an amyloid model …”

Section: Introductionmentioning

confidence: 99%

Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation

et al. 2023

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Neurodegenerative diseases are often associated with an uncontrolled amyloid aggregation. Hence, many studies are oriented to discover new compounds that are able to modulate self-recognition mechanisms of proteins involved in the development of these pathologies. Herein, three metal-complexes able to release carbon monoxide (CORMs) were analyzed for their ability to affect the self-aggregation of the amyloidogenic fragment of nucleophosmin 1, corresponding to the second helix of the three-helix bundle located in the C-terminal domain of the protein, i.e., NPM1264–277, peptide. These complexes were two cymantrenes coordinated to the nucleobase adenine (Cym-Ade) and to the antibiotic ciprofloxacin (Cym-Cipro) and a Re(I)-compound containing 1,10-phenanthroline and 3-CCCH2NHCOCH2CH2-6-bromo-chromone as ligands (Re-Flavo). Thioflavin T (ThT) assay, UV–vis absorption and fluorescence spectroscopies, scanning electron microscopy (SEM), and electrospray ionization mass spectrometry (ESI-MS) indicated that the three compounds have different effects on the peptide aggregation. Cym-Ade and Cym-Cipro act as aggregating agents. Cym-Ade induces the formation of NPM1264–277 fibers longer and stiffer than that formed by NPM1264–277 alone; irradiation of complexes speeds the formation of fibers that are more flexible and thicker than those found without irradiation. Cym-Cipro induces the formation of longer fibers, although slightly thinner in diameter. Conversely, Re-Flavo acts as an antiaggregating agent. Overall, these results indicate that metal-based CORMs with diverse structural features can have a different effect on the formation of amyloid fibers. A proper choice of ligands attached to metal can allow the development of metal-based drugs with potential application as antiamyloidogenic agents.

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