A Metalloporphyrin‐Peptide Conjugate as an Effective Inhibitor of Amyloid‐β Peptide Fibrillation and Cytotoxicity. Issue 28 (5th October 2017)

• Record Type: Journal Article
• Authors: Villari, Valentina; Tosto, Rita; Di Natale, Giuseppe; Sinopoli, Alessandro; Tomasello, Marianna F.; Lazzaro, Serena; Micali, Norberto; Pappalardo, Giuseppe
• Is Part Of: ChemistrySelect. Volume 2:Issue 28(2017)
• Page Start: 9122
• Page End: 9129
• Publication Date: 2017-10-05
• Subjects: Amyloid aggregation -- Porphyrin derivative -- Supramolecular recognition -- Toxicity inhibition; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201701148
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Molecules that inhibit Aβ misfolding have received considerable attention in view of their potential use in the prevention or treatment of Alzheimer's disease. We designed a peptide‐porphyrin conjugate incorporating two recognition sites enabling it to interact strongly with the Aβ42 peptide. The inhibitory effect on Aβ42 fibril formation was determined in aqueous solution by a variety of spectroscopic techniques including UV‐vis, fluorescence, Circular Dichroism, Dynamic Light Scattering, Maldi‐Time of Flight‐Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. A working mechanism of the antifibrillogenic action of the conjugate was proposed based on the experimental observations. The neuroprotective activity of the conjugate was also inferred by using primary neuronal or neuron‐like differentiated SH‐SY5Y cell cultures. Abstract : The reported porphyrin‐peptide derivative exhibits enhanced amyloid suppression properties, as well as inhibition of the cytotoxic effects of Aβ42, by generating non‐amyloidogenic aggregated forms. From the results, an important contribution of the metallo‐porphyrin moiety is apparent for the Aβ42 recognition. The whole of the evidence collected in this work proposes the reported compound as a potentially useful theranostic agent in AD.