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

Abstract

The conformation of tolylureas was studied by means of X-ray diffraction, NMR spectroscopy and semiempirical quantum-mechanical calculations. The flat shape of m- and p-isomers allows a good interaction with the model sites for bitter and sweet taste, respectively, whereas the o-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, is emphasized by the good fit of dulcin, a sweeter p-substituted arylurea.