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The known solid-state structure of cyclo(β-HAla)4 was used to model the structure of the cyclo-β-tetrapeptide (β-HPhe-β-HThr-β-HLys-β-HTrp) as a prospective somatostatin mimic. The synthesis started with the N-protected natural amino acids Boc-Phe-OH, Boc-Trp-OH, Boc-Lys(2-Cl-Z)-OH (2-Cl-Z = o-chlorobenzyloxycarbonyl), and Boc-Thr(OBn)-OH (Bn = benzyl), which were homologated to the corresponding β-amino-acid derivs. and coupled to the β-tetrapeptide Boc-β-HTrp-β-HPhe-β-HThr(OBn)-β-HLys(2-Cl-Z)-OMe. The (N-Me)-β-HThr-(N-Me)-β-HPhe analog was also prepd. C- and N-terminal deprotection and cyclization through the pentafluorophenyl ester gave the insol. beta-tetrapeptide with protected Thr and Lys side chains. Solubilization and debenzylation could only be effected in LiCl-contg. THF (ca. 10% yield; with ca. 55% recovery). HPLC Purifn. provided a sample of the title compd., the structure of which, as detd. by NMR-spectroscopy, was drastically different from the "theor." model. There is a transannular H-bond dividing the macrocyclic 16-membered ring, thus forming a ten- and a twelve-membered H-bonded ring, the former mimicking, or actually being superimposable on, an alpha-peptide so-called beta-turn. The four side chains occupy equatorial positions on the ring, as planned, albeit with somewhat different geometry as compared to the "original". The cyclo-β-tetrapeptide has micromolar affinities to the human somatostatin receptors. Thus, we have demonstrated for the first time that it is possible to mimic a natural peptide hormone with a small beta-peptide. Furthermore, we have discovered a simple way to construct the ubiquitous beta-turn motif with beta-peptides (which are known to be stable to mammalian peptidases).