Catechol: A minimal scaffold for non-peptide peptidomimetics of the i + 1 and i + 2 positions of the beta-turn of somatostatin.

The design, synthesis, and evaluation of a series of catechol-based non-peptide peptidomimetics of the peptide hormone somatostatin have been achieved. These ligands comprise the simplest known non-peptide mimetics of the i + 1 and i + 2 positions of the somatostatin beta-turn. Incorporation of an additional side chain to include the i position of the beta-turn induces a selective 9-fold affinity enhancement at the sst2 receptor.

Design and synthesis of potent cystine-free cyclic hexapeptide agonists at the human urotensin receptor.

[structure: see text] Cyclic hexapeptides, incorporating a dipeptide unit in place of the disulfide bond found in urotensin, were prepared and screened at the human urotensin receptor. The bridging dipeptide unit was found to influence dramatically the affinity for the urotensin receptor. Alanyl-N-methylalanyl and alanylprolyl dipeptide bridges failed to afford active ligands, while the alanyl-alanyl unit yielded a ligand with submicromolar affinity for the urotensin receptor. Further development led to a hexapeptide agonist with nanomolar affinity (2.8 nM).