Novel aspects of structure-activity relationships in sweet taste chemoreception

Abstract Although sweetness is exhibited by diverse chemical structures, structure-activity relationships within one class have been strictly limited. Across classes the only worthwhile approach has been the search for common AH,B glucophores which seem sufficient to confer the quality of sweetness. Increased intensity of sweetness demands a degree of lipophilicity and the more imaginative of the recently proposed models of sweet taste chemoreception have attempted to relate sweetness to molecular hydrophile-lipophile balance. All of these structure-activity approaches lack predictive power because they fail to take account of the real hydrated state of sweet molecules as they approach and accede to a sweet receptor site. A modern approach to structure-activity studies rests on the assumption that receptors are normally in a state of interaction with water molecules so that quantitative relationships between molecules must be derived from their aqueous solution properties. By examining the solution properties of defined structures, the effects of chain length and molecular fragments can be individually elucidated. Correlation of solution parameters with time-intensity sensory analyses allows inferences about the real size of molecules which elicit sweetness. Such data are shown to have a predictive value for both taste quality and sweetness potency.