A Metalloporphyrin-Peptide Conjugate as an Effective Inhibitor of Amyloid-β Peptide Fibrillation and Cytotoxicity

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.