An Extended β-Strand Mimic for a Larger Artificial β-Sheet

Abstract

This paper reports the development of β-strand mimic B, which duplicates the hydrogen-bonding functionality of one edge of a tetrapeptide β-strand. When attached to a tripeptide by a suitable linking group, β-strand mimic B forms a hydrogen-bonded antiparallel β-sheet structure, artificial β-sheet 2. β-Strand mimic B is based upon a 5-hydrazino-2-methoxybenzoic acid building block. The first half of the paper describes synthetic, IR and 1H NMR spectroscopic, X-ray crystallographic, and molecular modeling studies of 5-hydrazino-2-methoxybenzoic acid derivatives and related molecules. These studies establish that hydrazide derivatives of 5-hydrazino-2-methoxybenzoic acid adopt a conformation similar to that of a peptide β-strand and are suitable for use as β-strand mimics. The second half of the paper describes synthetic and 1H NMR spectroscopic studies of artificial β-sheet 2 and of controls 20 and 21, which resemble the peptidomimetic and peptide strands of 2. These experiments indicate that 2 adopts a conformation and hydrogen-bonding pattern similar to that of an antiparallel β-sheet and establish that β-strand mimic B can induce β-sheet formation in an attached peptide strand.