Fully automated synthesis of oxopiperazine helix mimics on Prelude^® X

This application note was authored by Professor Paramjit Arora and Dr. Ganesh Jedhe in the Department of Chemistry at New York University.

Protein−protein interactions are often mediated by amino acid side chain functionality organized on secondary structures. Small molecule scaffolds that reproduce the array of protein-like functionality at interfaces offer an attractive approach to target therapeutically important interactions. We have described the design, synthesis and biological potential of small molecule helix mimetics derived from an oxopiperazine scaffold to target protein complexes in which binding is largely dictated by one face of the interfacial helix. Here we describe a fully automated solid phase synthesis of oxopiperazine helix mimics (OHMs) from α-amino acids using a standard Fmoc solid-phase peptide synthesis methodology, enabling rapid diversification of the scaffold and discovery of ligands for protein targets. 

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