Solid-Phase Synthesis of Artificial β-Sheets

Abstract

This paper describes the solid-phase syntheses of artificial β-sheets 1−4, which mimic the structure and hydrogen-bonding patterns of protein β-sheets. In these compounds, molecular templates induce β-sheet structures in attached peptide strands. The templates consist of di- and triurea derivatives, which hold peptide and peptidomimetic strands in proximity, and β-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 β-sheets from the resin. The artificial β-sheets were prepared in 8−13 steps from leucine Merrifield in 33−67% overall yield.