Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes
Three Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1)<sub>264–277&...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/13/8/171 |
| _version_ | 1797560906719166464 |
|---|---|
| author | Daniele Florio Maria Cuomo Ilaria Iacobucci Giarita Ferraro Ahmed M. Mansour Maria Monti Antonello Merlino Daniela Marasco |
| author_facet | Daniele Florio Maria Cuomo Ilaria Iacobucci Giarita Ferraro Ahmed M. Mansour Maria Monti Antonello Merlino Daniela Marasco |
| author_sort | Daniele Florio |
| collection | DOAJ |
| description | Three Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1)<sub>264–277</sub>, a model amyloidogenic system, before and after irradiation at 365 nm. Thioflavin T (ThT) binding assays and UV/Vis absorption spectra indicate that binding of the compounds to the peptide inhibits its aggregation and that the inhibitory effect increases upon irradiation (half maximal effective concentration (EC<sub>50</sub>) values in the high micromolar range). Electrospray ionization mass spectrometry data of the peptide in the presence of one of these compounds confirm that the modulation of amyloid aggregation relies on the formation of adducts obtained when the Ru compounds react with the peptide upon releasing of labile ligands, like chloride and carbon monoxide. This mechanism of action explains the subtle different behavior of the three compounds observed in ThT experiments. Overall, data support the hypothesis that metal-based CO releasing molecules can be used to develop metal-based drugs with potential application as anti-amyloidogenic agents. |
| first_indexed | 2024-03-10T18:06:51Z |
| format | Article |
| id | doaj.art-3408f42cee084455b44555f64cf51d03 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T18:06:51Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3408f42cee084455b44555f64cf51d032023-11-20T08:25:39ZengMDPI AGPharmaceuticals1424-82472020-07-0113817110.3390/ph13080171Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) ComplexesDaniele Florio0Maria Cuomo1Ilaria Iacobucci2Giarita Ferraro3Ahmed M. Mansour4Maria Monti5Antonello Merlino6Daniela Marasco7Department of Pharmacy, University of Naples Federico II, 80134 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80134 Napoli, ItalyDepartment of Chemical Sciences, University of Naples Federico II, 80126 Napoli, ItalyDepartment of Chemistry Ugo Schiff, University of Florence, 50019 Sesto Fiorentino (FI), ItalyDepartment of Chemistry, Faculty of Science, University of Cairo, Gamma street, Giza 12613, EgyptDepartment of Chemical Sciences, University of Naples Federico II, 80126 Napoli, ItalyDepartment of Chemical Sciences, University of Naples Federico II, 80126 Napoli, ItalyDepartment of Pharmacy, University of Naples Federico II, 80134 Napoli, ItalyThree Ru(II)-based CO-releasing molecules featuring bidentate benzimidazole and terpyridine derivatives as ligands were investigated for their ability to modulate the aggregation process of the second helix of the C-terminal domain of nucleophosmin 1, namely nucleophosmin 1 (NPM1)<sub>264–277</sub>, a model amyloidogenic system, before and after irradiation at 365 nm. Thioflavin T (ThT) binding assays and UV/Vis absorption spectra indicate that binding of the compounds to the peptide inhibits its aggregation and that the inhibitory effect increases upon irradiation (half maximal effective concentration (EC<sub>50</sub>) values in the high micromolar range). Electrospray ionization mass spectrometry data of the peptide in the presence of one of these compounds confirm that the modulation of amyloid aggregation relies on the formation of adducts obtained when the Ru compounds react with the peptide upon releasing of labile ligands, like chloride and carbon monoxide. This mechanism of action explains the subtle different behavior of the three compounds observed in ThT experiments. Overall, data support the hypothesis that metal-based CO releasing molecules can be used to develop metal-based drugs with potential application as anti-amyloidogenic agents.https://www.mdpi.com/1424-8247/13/8/171modulators of amyloid peptide aggregationmetallodrugsruthenium(II) compoundsCO releasing molecules |
| spellingShingle | Daniele Florio Maria Cuomo Ilaria Iacobucci Giarita Ferraro Ahmed M. Mansour Maria Monti Antonello Merlino Daniela Marasco Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes Pharmaceuticals modulators of amyloid peptide aggregation metallodrugs ruthenium(II) compounds CO releasing molecules |
| title | Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes |
| title_full | Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes |
| title_fullStr | Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes |
| title_full_unstemmed | Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes |
| title_short | Modulation of Amyloidogenic Peptide Aggregation by Photoactivatable CO-Releasing Ruthenium(II) Complexes |
| title_sort | modulation of amyloidogenic peptide aggregation by photoactivatable co releasing ruthenium ii complexes |
| topic | modulators of amyloid peptide aggregation metallodrugs ruthenium(II) compounds CO releasing molecules |
| url | https://www.mdpi.com/1424-8247/13/8/171 |
| work_keys_str_mv | AT danieleflorio modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT mariacuomo modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT ilariaiacobucci modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT giaritaferraro modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT ahmedmmansour modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT mariamonti modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT antonellomerlino modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes AT danielamarasco modulationofamyloidogenicpeptideaggregationbyphotoactivatablecoreleasingrutheniumiicomplexes |