D-peptides are promising therapeutic agents because of their resistance to proteases and low immunogenicity. However, D-peptide discovery using high-throughput screening methods like mirror-image phage display requires chemical protein synthesis, CPS, of mirror-image target proteins, which previously limited such efforts to relatively small proteins.

Recent CPS advances like solubilizing "helping hands" and computational evaluation of potential synthesis pathways have greatly improved CPS efficiency and expanded its reach to larger target proteins.

Here we describe our progress in developing antiviral D-peptides, including an HIV entry inhibitor in clinical trials, as well as earlier-stage efforts to develop D-peptides targeting larger bacterial targets.