Synthesis and efficacy of dibenzofuran-based diacids and amino acids designed to nucleate parallel and antiparallel beta-sheet formation

In title, symbol for Greek letter beta is used.The synthesis of 4,6-dibenzofurandipropionic acid 18 and 4-(N-tertbutyloxycarbonyl-2-aminoethyl-)-6-dibenzofuranpropionic acid 19, designed to nucleate parallel and antiparallel (β-sheet formation respectively, was accomplished. Compounds 18 and 19 were incorporated into simple diamides and tetraamides in order to evaluate the potential of 18 and 19 to induce intramolecular hydrogen bonding interactions within the amide backbone. FT-IR, variable temperature NMR, and X-ray crystallography studies provided strong evidence for the expected intramolecular hydrogen bonding interactions. Circular dichroism analysis of a water soluble peptide having the sequence Val-Lys-Leu-19-Val-Lys-Leu-NH2 revealed the formation of a significant amount of β- sheet structure. Examination of a series of control peptides demonstrated that the presence of amino acid 19 was essential for (3-sheet structure formation