Fig. 1
Computational selection and SSTR profiling of consomatins from a large toxin gene dataset. (A) Principal component analysis (PCA) of 529 SST-like toxin sequences was used as the basis for selecting lead compounds for SSTR screening. Percentages refer to the proportion of the total variance in the data explained by the given principal component. A subset of the PCA plot, including vertebrate SS-like sequences and selected consomatins, is shown (right box). (B) Synthesized consomatin sequences selected from the PCA plot. Cleavage sites and post-translational modifications, such as D-Trp, were predicted based on the original somatostatin-like venom peptide, consomatin Ro1. Cysteines forming intramolecular disulfide bonds are shown in yellow and the essential Trp-Lys motif is highlighted in blue and green. Post-translational modifications are indicated by γ = γ-carboxyglutamate, w = D-Trp, O = hydroxyproline, and # = C-terminal amidation. SST-14 is human somatostatin-14. Seven of the listed sequences are from snails of the Asprella clade; Ro1 and Ro2 from C. rolani, Fj1, Fj2, and Fj3 from C. fijisulcatus, and SuSa1 and SuSa2 from C. sulcatus samiae, two are from the snails of the Phasmoconus clade; Oc3 from C. ochroleucus; Pr1 from C. parius, while pG1 was predicted from the transcriptome of C. geographus from the Gastridium clade16. (C) Heatmap of activity values of selected consomatins tested at the five human SSTRs using the PRESTO-Tango β-arrestin recruitment assay. Rows correspond to the sequences shown in (B). Data are represented as EC50 (top line, nanomolar, two significant digits shown) and pEC50 ± 95% confidence intervals (CI95) with the number of independent repeats in parentheses (bottom line, two significant decimals shown). Approximate values (~) or “higher than” (>) and “lower than” (<) are used when we did not obtain full curves within the concentrations tested (see Fig. S1 for representative curves).
