Pii: S0968-0896(98)00222-3

ÐThe aromatic diacid residue 4,6-dibenzofuranbispropionic acid (1) was designed to nucleate a parallel b-sheet-like structure in small peptides in aqueous solution via a hydrogen-bonded hydrophobic cluster. Even though a 14-membered ring hydrogen bond necessary for parallel b-sheet formation is favored in simple amides composed of 1, this hydrogen bonding interaction does not appear to be sucient to nucleate parallel b-sheet formation in the absence of hydrophobic clustering between the dibenzofuran portion of 1 and the hydrophobic side chains of the ̄anking a-amino acids. The subsequence -hydrophobic residue-1hydrophobic residueis required for folding in the context of a nucleated two-stranded parallel b-sheet structure. In all cases where the peptidomimetics can fold into two diastereomeric parallel b-sheet structures having di€erent hydrogen bonding networks, these conformations appear to exchange rapidly. The majority of the parallel b-sheet structures evaluated herein undergo linked intramolecular folding and self-assembly, a€ording a ®brillar b-sheet quaternary structure. To unlink folding and assembly, asymmetric parallel b-sheet structures incorporating N-methylated a-amino acid residues have been synthesized using a new solid phase approach. Residue 1 facilitates the folding of several peptides described within a€ording a monomeric parallel b-sheet-like structure in aqueous solution, as ascertained by a variety of spectroscopic and biophysical methods, increasing our understanding of parallel b-sheet structure. # 1999 Elsevier Science Ltd. All rights reserved.