A structure-activity study on the sucrose taste antagonist methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside

In order to assess the effect of the antagonist methyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside (MAD-diCl-Gal) upon the gerbil's chorda tympani sucrose taste response, we tested several concentrations of this compound, as well as single concentrations of closely related derivatives, and found that MAD-diCl-Gal was the most potent inhibitor tested. It appears that the inhibition mechanism is very specific. For example, we have found that 2 chlorine atoms at the C-4 and C-6 positions on the glucopyranoside ring are required for inhibition. In addition, with regard to the orientation of the chlorine atoms, the galacto derivative seems to be more potent than the gluco derivative. We have also found that the methyl glycoside is more potent than the free sugar. With regard to the orientation of the methyl group, MAD-diCl-Gal is more potent than its beta-anomer. (Because of this discovery of the methyl group enhancement and orientation effect, we shall discontinue using the acronym diCl-Gal and replace it with the more specific MAD-diCl-Gal.) Of particular significance is the fact that there appears to be a structure-activity relationship between the most active stimulants and inhibitors in that the requirement for an axial orientation at C-1 and the enhancement by the methyl group at that position are the same in both cases. These results suggest that both the stimulator and the antagonist are acting at the same receptor site.(ABSTRACT TRUNCATED AT 250 WORDS)