: 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.

Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation / La Manna, Sara; Roviello, Valentina; Napolitano, Fabiana; Malfitano, Anna Maria; Monaco, Vittoria; Merlino, Antonello; Monti, Maria; Kowalski, Konrad; Szczupak, Łukasz; Marasco, Daniela. - In: INORGANIC CHEMISTRY. - ISSN 1520-510X. - 62:26(2023), pp. 10470-10480. [10.1021/acs.inorgchem.3c01522]

Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation

La Manna, Sara;Roviello, Valentina;Malfitano, Anna Maria;Monaco, Vittoria;Merlino, Antonello;Monti, Maria;Marasco, Daniela
2023

Abstract

: 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.
2023
Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation / La Manna, Sara; Roviello, Valentina; Napolitano, Fabiana; Malfitano, Anna Maria; Monaco, Vittoria; Merlino, Antonello; Monti, Maria; Kowalski, Konrad; Szczupak, Łukasz; Marasco, Daniela. - In: INORGANIC CHEMISTRY. - ISSN 1520-510X. - 62:26(2023), pp. 10470-10480. [10.1021/acs.inorgchem.3c01522]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/937563
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