Abstract
In the present paper we describe the synthesis, purification, single crystal x‐ray analysis, and nmr solution characterization, combined with restrained molecular dynamic simulations, of the cyclic hexapeptide cyclo‐(L‐Pro‐L‐Phe‐β‐Ala)~2~. The peptide was synthesized by classical solution methods and the cyclization of the free hexapeptide was accomplished in good yields in diluted methylene chloride solution using N,N‐dicyclohexyl‐carbodiimide. The compound crystallizes in the monoclinic space group P2~1~ from methanol‐dichloro‐methane solution. The two identical halves of the molecule adopt in the solid state two different conformations. One β‐Ala‐L‐Pro peptide bond is trans, while the second is cis. The molecule is present in dimethylsulfoxide d~6~ solutions as a mixture of conformational families. One of these corresponds to a C~2~ symmetrical molecule with both β‐Ala‐Pro cis peptide bonds, while the second major conformation is very similar to that observed in the solid state. All Pro‐Phe segments, both in the solid state and the symmetrical and unsym‐metrical solution conformations, display ϕ,ψ angles close to that of position i + 1 and i + 2 of type II β‐turns. In addition, the segments preceeded by a trans β‐Ala‐Pro peptide bond are characterized by a typical i ← i + 3 hydrogen bond, which is absent in the conformer containing a cis β‐Ala‐Pro peptide bond. The latter conformation corresponds to a new structural domain we define as the “pseudo type II β‐turn.” © 1994 John Wiley & Sons, Inc.