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Pure Appl. Chem., 2002, Vol. 74, No. 7, pp. 1181-1187

Isovanillyl sweeteners. From molecules to receptors

Angela Bassoli, Lucio Merlini* and Gabriella Morini

Dipartimento di Scienze Molecolari Agroalimentari, Universitá di Milano, Via Celoria 2, 20133 Milano, Italy

Abstract: Systematic modification of the structure of the sweet natural compound phyllodulcin, containing the isovanillyl glucophoric group, led to the synthesis of about 120 compounds. Features of the heterocyclic ring conferring high sweetness potency were identified. A strong increase in sweetness was obtained by the introduction of sulfur atoms in the ring and by separation of the enantiomers. Results of the quantitative structure­activity relationship (QSAR) studies on this series are reported. Application of the pseudoreceptor modeling approach afforded a three-dimensional binding site model for isovanillyl sweeteners. Extension of this methodology to a large group of structurally diverse compounds, including the commonly used sweeteners, gave a general pseudoreceptor for the sweet compounds, consisting of 16 amino acids. This pseudoreceptor, which has the peculiarity of giving a semiquantitative evaluation of the sweetness intensity, could be used as a valid tool to model the ligand­receptor interactions and to suggest some clues about the identification of a possible binding site once the receptor protein(s) are obtained.