Abstracg 4-Wtert -butyloxycarbonyl-2-aminoethyl-)-6-dibenzofuranpropionic acid (1) and 4,6dibenzofumndipmpionic acid (2> designed to nucleate antiparallel and parallel g-sheet formation, respectively, have been synthesized in multi-gram quantities. Our understanding of parallel and antiparallel g-sheet secondary struchue in peptides and proteins lags significantly behind our comprehension of the a-helical sttucture because the development of p-sheet model systems have proven elusive. The inability to predict the locations of the required reverse turns or loops ( the turn problem ) and the tendency of g-sheets to aggregate, once formed, are impeding progress towards a well characterized g-sheet model system. 1 Nucleation of sheet formation may involve the formation of two intramolecular hydrogen bonds between residues i and i+3, hence, the torsion angles for the intervening residues must be restricted and compatible with this hydrogen bonding geometry (Fig la).
Nucleation is most likely the slowest and energetically most unfavorable step involved in g-sheet folding.
We have begun to address the turn problem by employing an unnatural dibenzofuran-based reverse turn having restricted conformational entropy and the appropriate geometry to nucleate hydrogen bond formation between strands at the optimal 4.gSA distance. We have, therefore, synthesized a simple conformationally restricted amino acid 1 and a diacid 2 in order to examine their potential to nucleate the formation of antiparallel and parallel g-sheet structures, respectively.