Molecular Mechanics of Cyclopropane Peptide Analogs of Aspartame

Molecular mechanics calculations on conformationally restricted cyclopropane peptide analogs of aspartame were used to develop a model for their binding to the sweet taste receptor, in which the ester alkyl group of the active analogs (aspartyl-1-aminocyclopropane carboxylic acid esters, Asp-Acc-OR) binds to the same site as the phenyl group of aspartame. The two possibilities for the active conformation correspond to the Temussi and Goodman models for the sweet taste receptor. The conformational restrictions imposed by incorporating isomers of 2,3- methanophenylalanine or 2,3-methanoproline into aspartame analogs are shown to be incompatible with either of these models, explaining their lack of sweet taste.