Supramolecular antiparallel β-sheet formation by tetrapeptides based on amyloid Sequence

Self-assembly of short peptides has emerged as an interesting research field for a wide range of applications. Recently, several truncated fragments of long-chain peptides or proteins responsible for different neurodegenerative diseases were studied to understand whether they can mimic the property and function of native peptides or not. It was reported that such a kind of peptide adopts a β-sheet structure in the disease state. It was observed that aromatic amino acid-rich peptide fragments possess a high tendency to adopt a β-sheet conformation. In this article, we are first time reporting the crystal structure of two tetrapeptides: Boc-GAII-OMe (Peptide 1) and Boc-GGVV-OMe (Peptide 2), composed of aliphatic amino acids, and the sequences are similar to the Aβ-peptide fragments Aβ29-32 and Aβ37-40 , respectively. In the solid-state, they are self-assembled in an antiparallel β-sheet fashion. The peptide units are connected by the strong amide hydrogen-bonding (N-H···O) interactions. Apart from that, other noncovalent interactions are also present, which help to stabilize the cross-β-sheet arrangement. Interestingly, in the crystal structure of Peptide 1, noncovalent C···C interaction between the electron-deficient carbonyl carbon, and the electron-rich sp3-carbon atom is observed, which is quite rare in the literature. The calculated torsion angles for these peptides are lying in the β-sheet region of the Ramachandran plot. FT-IR studies also indicate the formation of an antiparallel β-sheet structure in the solid-state. Circular dichroism of the peptides in the aqueous solution also suggests the presence of predominantly β-sheet-like conformation in the aqueous solution. Under cross-polarized light, Congo Red stained both peptides showed green-gold color due to birefringence indicating their amyloidogenic nature. This result indicates that the short peptide composed of aliphatic amino acid is capable of forming a β-sheet structure in the absence of aromatic amino acid and also can mimic the function of the native amyloid peptide.