Cationic porphyrins are reversible proteasome inhibitors (657 views)
J Am Chem Soc (ISSN: 0002-7863, 0002-2786, 1520-5126), 2012 Jun 27; 134(25): 10451-10457.
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Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 10.677, 5-year impact factor: 10.237
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84863490720&partnerID=40&md5=504f1817a8bdc96bcee859fd239e8b72
Keywords: Anticancer Properties, Axial Coordination, Cationic Porphyrin, Central Metals, Inhibition Activity, Inhibition Assays, Inhibitory Effect, Macrocycles, Metalloporphyrins, Micromolar Range, Molecular Levels, Peptidase Activity, Protease Activities, Proteasome Inhibitors, Spectroscopic Characterization, Uv-Vis Spectra, Water-Soluble Porphyrin, Dyes, Metal Ions, Scaffolds, Anion, Antineoplastic Agent, Cationic Porphyrin Derivative, Macrocyclic Compound, Proteinase, Unclassified Drug, Amino Terminal Sequence, Article, Canonical Analysis, Cell Assay, Controlled Study, Drug Activity, Drug Effect, Drug Efficacy, Drug Protein Binding, Drug Structure, Drug Targeting, Enzyme Activity, Human, Human Cell, Molecular Docking, Protein Structure, Protein Subunit, Static Electricity, Ultraviolet Radiation, Enzyme Activation, Enzyme Inhibitors, Hela Cells, Models, Proteasome Endopeptidase Complex, Cations Pharmacology, Enzyme Activation Drug Effects, Enzyme Inhibitors Pharmacology, Porphyrins Pharmacology,
Affiliations:
*** IBB - CNR ***
IBB-CNR, Istituto di Biostrutture e Bioimmagini, UOS di Catania C/o Dipartimento di Scienze Chimiche, Viale A. Doria 6, 95125 Catania, Italy
ISE-CNR, Istituto per Lo Studio Degli Ecosistemi, Largo Tonolli, 50, 28922 Verbania Pallanza (VB), Italy
Department of Periodontology and Biomaterials, Radboud University Nijmegen Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, Netherlands
References:
Not available.
J Am Chem Soc (ISSN: 0002-7863, 0002-2786, 1520-5126), 2012 Jun 27; 134(25): 10451-10457.
Export to BibTeX Export to EndNote
Paper type: Journal Article, Research Support, Non-U. S. Gov'T,
Impact factor: 10.677, 5-year impact factor: 10.237
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-84863490720&partnerID=40&md5=504f1817a8bdc96bcee859fd239e8b72
Keywords: Anticancer Properties, Axial Coordination, Cationic Porphyrin, Central Metals, Inhibition Activity, Inhibition Assays, Inhibitory Effect, Macrocycles, Metalloporphyrins, Micromolar Range, Molecular Levels, Peptidase Activity, Protease Activities, Proteasome Inhibitors, Spectroscopic Characterization, Uv-Vis Spectra, Water-Soluble Porphyrin, Dyes, Metal Ions, Scaffolds, Anion, Antineoplastic Agent, Cationic Porphyrin Derivative, Macrocyclic Compound, Proteinase, Unclassified Drug, Amino Terminal Sequence, Article, Canonical Analysis, Cell Assay, Controlled Study, Drug Activity, Drug Effect, Drug Efficacy, Drug Protein Binding, Drug Structure, Drug Targeting, Enzyme Activity, Human, Human Cell, Molecular Docking, Protein Structure, Protein Subunit, Static Electricity, Ultraviolet Radiation, Enzyme Activation, Enzyme Inhibitors, Hela Cells, Models, Proteasome Endopeptidase Complex, Cations Pharmacology, Enzyme Activation Drug Effects, Enzyme Inhibitors Pharmacology, Porphyrins Pharmacology,
Affiliations:
*** IBB - CNR ***
IBB-CNR, Istituto di Biostrutture e Bioimmagini, UOS di Catania C/o Dipartimento di Scienze Chimiche, Viale A. Doria 6, 95125 Catania, Italy
ISE-CNR, Istituto per Lo Studio Degli Ecosistemi, Largo Tonolli, 50, 28922 Verbania Pallanza (VB), Italy
Department of Periodontology and Biomaterials, Radboud University Nijmegen Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, Netherlands
References:
Not available.
Cationic porphyrins are reversible proteasome inhibitors
The aim of this study is to verify if water-soluble porphyrins can be used as proteasome inhibitors. We have found that cationic porphyrins inhibit proteasome peptidase activities much more effectively than the corresponding anionic derivatives. The relevance of electrostatics in driving porphyin-proteasome interactions has been confirmed by the observation that the inhibitory efficiency of the cationic macrocycles decreases with the number of positive substituents. We have also investigated various metalloporphyrins, which differ due to the different propension of the central metal ion toward axial coordination. Our experimental results indicate that the naked cationic porphyrins are the most active in reversibly inhibiting the three main protease activities of the proteasome in the micromolar range. A spectroscopic characterization of porphyrin-proteasome interactions by UV-vis spectra parallels the results of inhibition assays: the higher the inhibitory effect the stronger the spectroscopic variations are. To interpret the action of porphyrins at a molecular level, we have performed calculations evidencing that cationic porphyrins may hinder the access to the canonical proteolytic site on the proteasome β5 subunit. In particular, an inspection of the top-scoring docking modes shows that the tetracationic porphyrin blocks the catalytic pocket, close to the N termini of the β5 proteasome subunit, more efficiently than its anionic counterpart. Proteasome inhibition activity of porphyrins unites their known anticancer properties making them suitable as a scaffold for the design of novel multitargeted molecules. © 2012 American Chemical Society.
The aim of this study is to verify if water-soluble porphyrins can be used as proteasome inhibitors. We have found that cationic porphyrins inhibit proteasome peptidase activities much more effectively than the corresponding anionic derivatives. The relevance of electrostatics in driving porphyin-proteasome interactions has been confirmed by the observation that the inhibitory efficiency of the cationic macrocycles decreases with the number of positive substituents. We have also investigated various metalloporphyrins, which differ due to the different propension of the central metal ion toward axial coordination. Our experimental results indicate that the naked cationic porphyrins are the most active in reversibly inhibiting the three main protease activities of the proteasome in the micromolar range. A spectroscopic characterization of porphyrin-proteasome interactions by UV-vis spectra parallels the results of inhibition assays: the higher the inhibitory effect the stronger the spectroscopic variations are. To interpret the action of porphyrins at a molecular level, we have performed calculations evidencing that cationic porphyrins may hinder the access to the canonical proteolytic site on the proteasome β5 subunit. In particular, an inspection of the top-scoring docking modes shows that the tetracationic porphyrin blocks the catalytic pocket, close to the N termini of the β5 proteasome subunit, more efficiently than its anionic counterpart. Proteasome inhibition activity of porphyrins unites their known anticancer properties making them suitable as a scaffold for the design of novel multitargeted molecules. © 2012 American Chemical Society.
Cationic porphyrins are reversible proteasome inhibitors
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Cationic porphyrins are reversible proteasome inhibitors
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Santoro AM, D’urso A, Cunsolo A, Milardi D, Purrello R, Sbardella D, Tundo GR, Diana D, Fattorusso R, Di Dato A, Paladino A, Persico M, Coletta M, Fattorusso C
* Cooperative binding of the cationic porphyrin tris-t4 enhances catalytic activity of 20s proteasome unveiling a complex distribution of functional states (153 views)
Int J Mol Sci (ISSN: 1422-0067linking), 2020 Sep 29; 21(19): N/D-N/D.
Impact Factor: 0
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D’errico S, Falanga AP, Capasso D, Di Gaetano S, Marzano M, Terracciano M, Roviello GN, Piccialli G, Oliviero G, Borbone N
* Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex (176 views)
Pharmaceutics (ISSN: 1999-4923linking, 1999-4923electronic), 2020 Jul 4; 12(7): 627-627.
Impact Factor: 4.421
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Tomasello MF, Nardon C, Lanza V, Di Natale G, Pettenuzzo N, Salmaso S, Milardi D, Caliceti P, Pappalardo G, Fregona D
* New comprehensive studies of a gold(III) Dithiocarbamate complex with proven anticancer properties: Aqueous dissolution with cyclodextrins, pharmacokinetics and upstream inhibition of the ubiquitin-proteasome pathway (931 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2017 Jun 19; 138: 115-127.
Impact Factor: 4.816
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Gaglione R, Pirone L, Farina B, Fusco S, Smaldone G, Aulitto M, Dell'Olmo E, Roscetto E, Del Gatto A, Fattorusso R, Notomista E, Zaccaro L, Arciello A, Pedone E, Contursi P
* Insights into the anticancer properties of the first antimicrobial peptide from Archaea (466 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 0304-4165linking), 2017 Jun 15; 1861(9): 2155-2164.
Impact Factor: 4.28
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Santoro AM, Cunsolo A, D'Urso A, Sbardella D, Tundo GR, Ciaccio C, Coletta M, Diana D, Fattorusso R, Persico M, Di Dato A, Fattorusso C, Milardi D, Purrello R
* Cationic porphyrins are tunable gatekeepers of the 20S proteasome (764 views) (PDF 242 views)
Chem Sci (ISSN: 2041-6520, 2041-6520linking, 2041-6520print), 2016; 7(2): 1286-1297.
Impact Factor: 8.668
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Sandomenico A, Celentano V, D'Andrea LD, Palmieri G, Ruvo M
* Screening of beta-hairpin peptide-engrafted 1, 2, 3-triazoles to identify APEH enzyme inhibitors (483 views)
Rsc Adv (ISSN: 2046-2069, 2046-2069electronic), 2015; 5(13): 9965-9972.
Impact Factor: 3.289
View Export to BibTeX Export to EndNote
* Cooperative binding of the cationic porphyrin tris-t4 enhances catalytic activity of 20s proteasome unveiling a complex distribution of functional states (153 views)
Int J Mol Sci (ISSN: 1422-0067linking), 2020 Sep 29; 21(19): N/D-N/D.
Impact Factor: 0
View Export to BibTeX Export to EndNote
D’errico S, Falanga AP, Capasso D, Di Gaetano S, Marzano M, Terracciano M, Roviello GN, Piccialli G, Oliviero G, Borbone N
* Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex (176 views)
Pharmaceutics (ISSN: 1999-4923linking, 1999-4923electronic), 2020 Jul 4; 12(7): 627-627.
Impact Factor: 4.421
View Export to BibTeX Export to EndNote
Tomasello MF, Nardon C, Lanza V, Di Natale G, Pettenuzzo N, Salmaso S, Milardi D, Caliceti P, Pappalardo G, Fregona D
* New comprehensive studies of a gold(III) Dithiocarbamate complex with proven anticancer properties: Aqueous dissolution with cyclodextrins, pharmacokinetics and upstream inhibition of the ubiquitin-proteasome pathway (931 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2017 Jun 19; 138: 115-127.
Impact Factor: 4.816
View Export to BibTeX Export to EndNote
Gaglione R, Pirone L, Farina B, Fusco S, Smaldone G, Aulitto M, Dell'Olmo E, Roscetto E, Del Gatto A, Fattorusso R, Notomista E, Zaccaro L, Arciello A, Pedone E, Contursi P
* Insights into the anticancer properties of the first antimicrobial peptide from Archaea (466 views)
Bba-Gen Subjects (ISSN: 0005-2728, 0006-3002print, 0304-4165linking), 2017 Jun 15; 1861(9): 2155-2164.
Impact Factor: 4.28
View Export to BibTeX Export to EndNote
Santoro AM, Cunsolo A, D'Urso A, Sbardella D, Tundo GR, Ciaccio C, Coletta M, Diana D, Fattorusso R, Persico M, Di Dato A, Fattorusso C, Milardi D, Purrello R
* Cationic porphyrins are tunable gatekeepers of the 20S proteasome (764 views) (PDF 242 views)
Chem Sci (ISSN: 2041-6520, 2041-6520linking, 2041-6520print), 2016; 7(2): 1286-1297.
Impact Factor: 8.668
View Export to BibTeX Export to EndNote
Sandomenico A, Celentano V, D'Andrea LD, Palmieri G, Ruvo M
* Screening of beta-hairpin peptide-engrafted 1, 2, 3-triazoles to identify APEH enzyme inhibitors (483 views)
Rsc Adv (ISSN: 2046-2069, 2046-2069electronic), 2015; 5(13): 9965-9972.
Impact Factor: 3.289
View Export to BibTeX Export to EndNote
6 Records (6 excluding Abstracts).
Total impact factor: 25.474 (25.474 excluding Abstracts).
Total 5 year impact factor: 21.53 (21.53 excluding Abstracts).
Total impact factor: 25.474 (25.474 excluding Abstracts).
Total 5 year impact factor: 21.53 (21.53 excluding Abstracts).
657 views. Last view on Tuesday 24 September 2024, 20:55:59
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