Journal article

Peptide folding induces high and selective affinity of a linear and small β-peptide to the human somatostatin receptor 4

β-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 β-turn). Thus, the authors have synthesized an appropriately substituted β-tetrapeptide deriv. to mimic the hormone somatostatin in its binding to the human receptors hsst1-5, which is known to rest upon a turn contg. the amino acid residues Thr, Lys, Trp, and Phe. The N-acetyl-peptide amide Ac-β3-HThr-β2-HLys-β3-HTrp-β3-HPhe-NH2 indeed shows all characteristics of the targeted turn-mimic: Lys CH2 groups are in the shielding cone of the Trp indole ring (by NMR anal.) and there is high and specific nanomolar affinity for hsst4 receptor. 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 hsst4. The syntheses of the required Fmoc-protected β-amino acids are described. Coupling of the β-amino acids was achieved by the manual solid-phase technique, on Rink resin.


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