Engineering of Supramolecular β-Sheet and Nontoxic Amyloid Fibrils from Synthetic Oligopeptides Containing γ-Aminobutyric Acid as the N-Terminal Residue.

Abstract

Here we demonstrate that three synthetic tripeptides containing conformationally flexible γ-aminobutyric acid (γ-Abu) as the N-terminal residue form supramolecular β-sheet and nanofibrillar aggregates upon self-association in aqueous medium. Congo red and thioflavin T binding study establish that these nanofibrillar aggregates are amyloidogenic in nature. The MTT cell survival assay suggests that these amyloid-like nanofibrillar aggregates are nontoxic toward cultured Neuro 2A cells. Interestingly, none of these tripeptides bear sequence identity with any amyloid forming proteins or peptides; however upon self-association, they form supramolecular β-sheet and amyloid-like nanofibrils those are nontoxic in nature. The results highlight the self-assembling nature of the conformationally flexible peptides in aqueous environment and support the hypothesis that amyloid formation is the intrinsic property of the polypeptide chain. Also the cytotoxicity is not predictive from amyloid fibril formation alone. Such nontoxic amyloid fibrils can be exploited in future to design functional biomaterials for various biomedical applications.