Interaction of conformationally flexible agonists with the active site of sweet taste. A study of arylureas.

The conformation of tolylureas has been studied by means of X-ray diffraction, NMR spectroscopy, and semiempirical quantum-mechanical calculations. The flat shape of meta and para isomers allows a good interaction with the model sites for bitter and sweet taste, respectively, whereas the ortho isomer cannot fit the sites because of the relative arrangements of the aryl and amide planes and because of poor hydrophobic interactions. The consistency of the conformational results with the sweet taste model site, previously proposed by the authors, is emphasized by the good fit of dulcine, a sweeter para-substituted arylurea.