β‐Alanine containing cyclic peptides with predetermined turned structure.

In the present paper we describe the synthesis, purification, single crystal x-ray analysis, and solution structural characterization by nmr spectroscopy, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo-(Pro-Phe-β-Ala-Phe-Phe-β-Ala). The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylenechloride solution using N, N-dicyclohexyl-carbodiimide. The compound crystallizes in the monoclinic space group P21 from methanol/ethyl acetate. The molecule adopts in the solid state a conformation characterized by cis β-Ala6-Pro1 peptide bond. The α-amino acid residues are at the corner positions of turned structures. The Pro1-Phe2 segment is incorporated in a pseudo type I β-turn, while Phe4-Phe5 is in a typical type I β-turn.