Design, Synthesis and Evaluation of Unnatural Peptides as T1R2/T1R3 PAMs
2020
Abstract The sweet receptor T1R2/T1R3 is a member of G protein-coupled receptor family and recognizes diverse natural and synthetic sweeteners. Previously, we reported a novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 comprising an unnatural tripeptide structure. We classified the structure of these PAMs into three parts: “head”, “linker” and “tail”. Here, we report the design, synthesis and evaluation of various tail structures to obtain highly active unnatural peptide structure of PAM. In conclusion, we discovered the novel unnatural tetrapeptide with highly potent PAM activity on T1R2/T1R3 in a cell-based assay system.
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