Solid-phase synthesis of artificial beta-sheets

This paper describes the solid-phase syntheses of artificial beta-sheets 1-4, which mimic the structure and hydrogen-bonding patterns of protein beta-sheets. In these compounds, molecular templates induce beta-sheet structures in attached peptide strands. The templates consist of di-and triurea derivatives, which hold peptide and peptidomimetic strands in proximity, and beta-strand mimics, which hydrogen bond to the peptide strands. The syntheses involve constructing the ''lower'' peptide strand on Merrifield resin, attaching the di-or triamine portions of the di-or triurea templates, connecting the ''upper'' peptide and peptidomimetic strands, and cleaving the resulting artificial beta-sheets from the resin. The artificial beta-sheets were prepared in 8-13 steps from leucine Merrifield in 33-67% overall yield.