As a demonstration, potent binders with low-to-subnanomolar K D values were identified for human factor XIIa (hFXIIa) and interferon-gamma receptor 1, from a library of their 10 12 members. We also report the de novo discovery of macrocyclic cβAA-containing peptides capable of binding to a protein target. Here we report the ribosomal synthesis of foldamer peptides that contain multiple, up to ten, consecutive cβAAs via genetic code reprogramming. Cyclic β 2,3-amino acids (cβAAs), such as 2-aminocyclohexanecarboxylic acid (2-ACHC), are strong helix/turn inducers due to their restricted conformations. Peptides that contain β-amino acids display stable secondary structures, such as helices and sheets, and are often referred to as foldamers.
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