Peroxynitrite scavenger FeTPPS effectively inhibits hIAPP aggregation and protects against amyloid induced cytotoxicity

Structure and mechanism behind the inhibitory effect of water soluble metalloporphyrins on Aβ1–42aggregation

“…Although compounds with a high aromaticity value may have the ability to inhibit the aggregation of amyloid peptides, 6,[38][39][40] and many of them have relatively low inhibition potency. For example, we recently found that FeTPPS and FeTBAP have a better inhibitory effect on human islet amyloid polypeptide (hIAPP) fibril formation, 25,26 whereas, FeTMPyP, a structural analogue of FeTPPS and FeTBAP, is less effective, 26 indicating that the inhibitory effect of these ironporphyrins on hIAPP aggregation has a structure-activity relationship. In addition, most of the amyloid inhibitors only work for a specific amyloid peptide and show sequence-dependent inhibition capacity.…”

“…We previously found that several metalloporphyrins have the ability to disaggregate hIAPP and Aβ 1-42 fibrils. 25,26,32,33 However, promoting Aβ 1-42 disaggregation may not always be optimal for the development of potential AD therapeutics, due to the formation of neurotoxic soluble Aβ 1-42 oligomers. 48 As shown in Fig.…”

“…22–24 However, from a chemical standpoint, these compounds are cyclic tetrapyrroles, a class of compounds whose distinguished characteristics are the planarity and hydrophobicity of their aromatic ring system, indicating that they may have the ability to inhibit amyloid polypeptide/protein aggregation. 25–29…”

“…[22][23][24] However, from a chemical standpoint, these compounds are cyclic tetrapyrroles, a class of compounds whose distinguished characteristics are the planarity and hydrophobicity of their aromatic ring system, indicating that they may have the ability to inhibit amyloid polypeptide/protein aggregation. [25][26][27][28][29] The development of metal compounds as potential agents capable of modifying and inhibiting Aβ aggregation is an emerging area in metal-based therapeutic drug design. 30,31 We and others found that heme significantly decreases amyloidogenic aggregation.…”

Introduction and Fundamentals of Human Islet Amyloid Polypeptide Inhibitors

“…The exact inhibition and disaggregation mechanisms of IV complexes on hIAPP remain unclear due to the lack of characterization of binding modes between IV complexes and hIAPP aggregates. FeTPPS, a water-soluble derivative of heme, remarkably affected hIAPP fibrillation by both stabilizing hIAPP monomers and disaggregating the long fibrils into small oligomeric species . In short, pharmacological chaperone O4, azadirachtin, chitosan oligosaccharides (COS), cyclen-NYGAIL-copper complex, α-aminoisobutyric acid (Aib) and its isomers, and penta- O -galloyl- d -glucopyranose (PGG) , can inhibit and disassemble hIAPP aggregates.…”