Fig. 5
Analog design and testing identified improved ligands for SSTR4-selective drug development. (A) Identifiers and sequences of SST-14, Fj1, and the analogs of Fj1. Sequences (left) show the Cys residues forming the intramolecular disulfide in Fj1 and its analogs highlighted in yellow. For all sequences, the Trp residue is shown in blue, the Lys residue in green, and all modifications in the analogs, as compared to Fj1, are highlighted in red. Sequences use standard amino acid one-letter abbreviations extended with O = hydroxyproline and lower-case letters denoting D-amino acids. (B) Heatmap showing the potency of Fj1 and its analogs at the five human SSTRs in the G protein dissociation assay using GαoA. The text in each cell represents the EC50 value (first line, nanomolar, two significant digits) and the pEC50 ± CI95 (two significant decimals) with the number of independent repeats for each in parentheses (second line). Approximate values (~) or “higher than” (>) and “lower than” (<) are used when we did not obtain full curves within the concentrations tested (see Fig. S3 for representative curves). The known SSTR1 and SSTR4 peptide agonist, TT-232 was also tested. However, we note that we could not dissolve it at sufficiently high concentrations to fully test this peptide in the assay used).
