Hydroxy‐Porphyrin as an Effective, Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization

Abstract

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation.Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis.

Synthesis of Fe3O4-Chlorophyllin Nanoparticles for Preventing Amyloid Formation by Human Calcitonin

“…Later, Nath et al evaluated the efficacy of endogenous porphyrin-based small molecules in preventing insulin and hen egg-white lysozyme amyloid formation. Hydroxylation of the heme moiety improves its inhibitory effectiveness . Two additional hydroxyl groups on the porphyrin-based structure provide hydrogen-bonding anchors to amyloidogenic proteins to block the protein self-assembly.…”

“…Hydroxylation of the heme moiety improves its inhibitory effectiveness. 20 Two additional hydroxyl groups on the porphyrin-based structure provide hydrogen-bonding anchors to amyloidogenic proteins to block the protein self-assembly. These findings indicate that porphyrin-based molecules have great potential against amyloidogenesis.…”