N-terminal extension of sweet peptides in relation to the structural features of peptide sweeteners.

Sweet aspartyl di- and tripeptide esters were extended toward the N-terminus in relation to the structural features of sweet peptides. The sweet peptides were designed on the basis of the receptor site model. It was found that an extension of the sweet aspartyl dipeptide esters by adding a small D-amino acid residue mostly gave sweet compounds (e.g., D-Ala-L-Asp-D-Ala-OMe), although this significantly decreased their sweetness potencies. Further extension at the N-terminus of the extended sweet tripeptide esters to yield the tetrapeptide esters resulted in a loss of the sweet taste. The N-terminal extension of sweet aspartyl tripeptide esters resulted in faintly sweet or nonsweet tetrapeptide esters. Interestingly, an analogous extension at the N-terminus of the sweet aminomalonyl dipeptide esters gave bitter compounds (e.g., D-Ala-DL-Ama-L-Phe-OMe). These results indicate that the receptor has a small space that can accomodate an additional small D-amino acid residue at the site facing the N-terminus of sweet aspartyl dipeptide esters.