Supramolecular β-Sheet and Nanofibril Formation by Self-assembling Tripeptides Containing an N-terminally Located γ-Aminobutyric acid Residue

Abstract

Three terminally protected tripeptides Boc–γ-Abu–Val–Leu–OMe 1, Boc–γ-Abu–Leu–Phe–OMe 2 and Boc–γ-Abu–Val–Tyr–OMe 3 (γ-Abu = γ-aminobutyric acid) each containing an N-terminally positioned γ-aminobutyric acid residue have been synthesized, purified and studied. FT-IR studies of all these peptides revealed that these peptides form intermolecularly hydrogen bonded supramolecular β-sheet structures. Peptides 1, 2 and 3 adopt extended backbone β-strand molecular structures in crystals. Crystal packing of all these peptides demonstrates that these β-strand structures self-assemble to form intermolecularly H-bonded parallel β-sheet structures. Peptide 3 uses a side chain tyrosyl –OH group as an additional hydrogen bonding functionality in addition to the backbone CONH groups to pack in crystals. Transmission electron microscopic studies of all peptides indicate that they self-assemble to form nanofibrillar structures of an average diameter of 65 nm. These peptide fibrils exhibit amyloid-like behavior as they bind to a physiological dye Congo red and show a characteristic green-gold birefringence under polarizing microscope.