Cationic Porphyrins Are Reversible Proteasome Inhibitors (Articolo in rivista)

Type
Label
  • Cationic Porphyrins Are Reversible Proteasome Inhibitors (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/ja300781u | (literal)
Alternative label
  • Anna Maria Santoro; Maria Cristina Lo Giudice; Alessandro D'Urso; Rosaria Lauceri; Roberto Purrello; Danilo Milardi (2012)
    Cationic Porphyrins Are Reversible Proteasome Inhibitors
    in Journal of the American Chemical Society (Online); ACS, American chemical society, Washington, DC (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Anna Maria Santoro; Maria Cristina Lo Giudice; Alessandro D'Urso; Rosaria Lauceri; Roberto Purrello; Danilo Milardi (literal)
Pagina inizio
  • 10451 (literal)
Pagina fine
  • 10457 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 134 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 7 (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Anna Maria Santoro, Rosaria Lauceri, Danilo Milardi, IBB-CNR, Istituto di Biostrutture e Bioimmagini, UOS di Catania. Maria Cristina Lo Giudice, Alessandro D'Urso, Roberto Purrello, Dipartimento di Scienze Chimiche, Universita? degli Studi di Catania. (literal)
Titolo
  • Cationic Porphyrins Are Reversible Proteasome Inhibitors (literal)
Abstract
  • The aim of this study is to verify if watersoluble 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 ?5 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 ?5 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. (literal)
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