π-System Functionalization Transforms Amyloidogenic Peptide Fragment of Human Islet Amyloid Polypeptide into a Super Hydrogelator

While a considerable number of ultra-short/short amyloid peptides have been reported to form 3D supramolecular hydrogels, they all possess high minimum gelation concentration (MGC) (>= 1 wt%), which preclude their applications. In this context, we demonstrate that functionalisation of a well-known amyloidogenic ultra-short peptide fragment NFGAIL (IAPf) of human Islet amyloid polypeptide with a pi-system (Fluorenyl, Fm) at the N-terminus of the peptide (Fm-IAPf) yield not only highly thermostable hydrogel at physiological pH but also exhibited super gelator nature as the MGC (0.08 wt%) falls below 0.1 wt%. Various experimental results confirmed that aromatic pi-pi interactions from fluorenyl moieties and hydrogen bonding interactions between the IAPf drive the self-assembly/fibril formation. Fm-IAPf is the first super hydrogelator derived from amyloid-based ultra-short peptides, to the best of our knowledge. We strongly believe that this report, i. e., functionalization of an amyloid peptide with pi-system, provides a lead to develop super hydrogelators from other amyloid-forming peptide fragments for their potential applications.

Automated summary

By functionalizing a pi-system (Fluorenyl, Fm) at the N-terminus of the well-known amyloidogenic ultra-short peptide fragment NFGAIL (IAPf) of human Islet amyloid polypeptide, we obtained a highly thermostable hydrogel at physiological pH with a super gelator nature (MGC 0.08 wt%). Various experimental results confirmed that the self-assembly/fibril formation is driven by aromatic pi-pi interactions from fluorenyl moieties and hydrogen bonding interactions between the IAPf. Fm-IAPf is the first super hydrogelator derived from amyloid-based ultra-short peptides, to the best of our knowledge, and we believe this report provides a lead for developing super hydrogelators from other amyloid-forming peptide fragments.