Design and Asymmetric Synthesis of β-Strand Peptidomimetics

Abstract

We describe the asymmetric synthesis of non-peptidic compounds that feature rigid backbone conformations and present various side-chain functions. The key step in the synthesis of these compounds is the C-acylation of an appropriate ketone with a suitably protected aspartic acid derivative. The resulting dipeptide modules may be connected to form tetrapeptide mimics. Specifically is described the mimicry of a four-residue segment of CD4, the cellular receptor of HIV-1. The design was based on molecular modeling and the X-ray crystal structures of CD4 and intended to present the most important side chains and backbone elements of the Phe43-Lys46 segment.