Biochemistry and Biotechnology
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-α-methylphenylalanine methyl ester [L-Asp-D-(αMe)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5,5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups formaing a zwitterionic ring with a conformation defined by ψ,χX1 = 157.7°, -61.5° for L-Asp-D-Ala-OTMCP and 151.0°, -68.8° for L-Asp-D-(αMe)Phe-OMe. In the second residue, a left-handed helical conformations is observed for the (αMe)Phe residue of L-Asp-D-(αMe)Phe-OMe with φ2 = 49.0° and ψ2 = 47.9°, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-exextended conformation characterized by dihedral angles φ2 = 62.8° and ψ2 = -139.9°. The solid-state structure of the bitter L-Asp-D-(αMe)Phe-OMe is extended; while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(αMe)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(αMe)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.
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