Peptide Sweeteners. 3. Effect of Modifying the Peptide Bond on the Sweet Taste of L-Aspartyl-L-Phenylalanine Methyl Ester and its Analogs

A series of analogues designed to assess the importance of the amide bond in the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester has been synthesized and tested. The peptide bond was methylated, replaced by an ester bond, or reversed. All of these modifications produced compounds that did not have a sweet taste. We conclude that the steric, electronic, and directional characteristics of the amide bond are essential for biological activity in the dipeptide sweeteners. © 1980, American Chemical Society. All rights reserved.