
<ArticleTitle>Peptide folding induces high and selective affinity of a linear and small beta-peptide to the human <prot>somatostatin receptor 4</prot>.</ArticleTitle>
<AbstractText>beta-Peptides with side chains in the 2- and 3-positions on neighboring residues (of (S) configuration) are known to fold and form a turn (similar to an alpha-peptidic beta-turn). Thus, we have synthesized an appropriately substituted beta-tetrapeptide derivative to mimic the hormone <prot>somatostatin</prot> in its binding to the human receptors <prot>hsst(1</prot>-5), which is known to rest upon a turn containing the amino acid residues Thr, Lys, Trp, and Phe. The N-acetyl-peptide amide Ac-beta(3)-HThr-beta(2)-HLys-beta(3)-HTrp-beta(3)-HPhe-NH(2) (1) indeed shows all characteristics of the targeted turn-mimic: Lys CH(2) groups are in the shielding cone of the Trp indole ring (by NMR analysis, Figure 2) and there is high and specific nanomolar affinity for <prot>hsst(4)</prot> receptor (Table 1). In contrast, the isomer 2 bearing the Lys side chain in 3-, rather than in the 2-position, has a 1000-fold smaller affinity to <prot>hsst(4)</prot>. The syntheses of the required Fmoc-protected beta-amino acids (8-11, 17) are described (Schemes 1-3). Coupling of the beta-amino acids was achieved by the manual solid-phase technique, on Rink resin.</AbstractText>
