Screening of FFAR1-Activating Peptides by Molecular Structural Analysis

To find FFAR1-activating peptides consisting of natural amino acid residues, molecular structure analysis was performed by hierarchical clustering using extraction of physicochemical parameters. When 3 mer to 6 mer peptide libraries were prepared and the molecular structure of each was compared with 5 chemical agonists, 12 peptides with high correlation coefficients of physicochemical parameters were found from the 6 mer peptide library. These peptides were then synthesized by Fmoc solid phase synthesis, and their activity was assessed by TGF alpha shedding assay using FFAR1-expressing HEK293. As a result, two peptides, GCGGSS and GASGCC, were identified as peptide agonists with relatively high activity. Although these peptides showed approximately one fifth of the activity of chemical agonist GW9508, they are the first examples that we know of FFAR1-activating peptides consisting of natural amino acid residues.

Automated summary

Hierarchical clustering was used to analyze the molecular structure of peptide libraries consisting of natural amino acid residues, leading to the identification of 12 peptides with high correlation coefficients. These peptides were synthesized and tested, resulting in the discovery of two peptide agonists with relatively high activity compared to a chemical agonist. These peptides represent the first known examples of FFAR1-activating peptides composed of natural amino acid residues.