Study of dibenzofuran-based amino acid nucleated antiparallel Beta-sheet using 1D- and 2D- nuclear magnetic resonance spectroscopy

Abstract

Simple amides containing the conforrnationally restricted unnatural amino acid 4-(2-aminoethyl)-6-dibenzofuranpropanoic acid (1) were studied by NMR and FT-IR to ascertain the hydrogen bonding capabilities of 1. The preferred structure in non-competitive solvents is a 15-membered ring hydrogen bonded conformation. Water soluble peptides containing 1 were studied using I D-and 2D-NMR techniques to determine the capability of 1 to nucleate 0-sheet structure formation. The sequence specific assigrunents of the peptides as well as the determination of the secondary structure was accomplished. In solution, at pH-5, both peptides exhibit a welldefined 0-tum structure with the dibenzofuran ring of 1 perpendicular to the plane of the strands, interacting with the hydrophobic side chains of the residues flanking it through a hydrophobic interaction, thus forming a well-defined 0-tum mimetic. This hydrophobic cluster also promotes the formation of the 15-membered ring hydrogen bonded conformation necessary for 0-sheet nucleation.