Incorporation of Stable Pseudopeptide Bonds: Methylene Amino, Thioether, and Hydroxyethylene Derivatives

The introduction of pseudopeptide bonds (amide bond surrogates) into the peptide backbone during synthesis is now a common technique in peptide chemistry (1). These pseudo-peptide bonds are introduced in order to satisfy criteria such as stability to enzymatic degradation, transition state analogs/enzyme inhibition, alteration in peptide backbone conformation (with corresponding changes in flexibility and hydrogen-bonding character), increased receptor specificity, increased potency, and biological responses (2).