Design of peptides: synthesis, crystal structure and molecular conformation of N-Boc-L-Val-delta Phe-L-Ile-OCH3.

The dehydro-peptide Boc-L-Val-delta Phe-L-Ile-OCH3 was synthesized by the azlactone method in the solution phase. The peptide crystallized from a methanol/dimethyl sulfoxide (95:5) mixture in space group P6(1) with a = b = 15.312(1), c = 22.164(5) A. The structure was determined by direct methods and refined to an R value of 0.098 for 1589 observed reflections [I > or = 1.5 sigma (I)]. The peptide adopts an S-shaped conformation with torsion angles: phi 1 = -127(1), psi 1 = -44(1), phi 2 = 67(1), psi 2 = 37(1), phi 3 = -82(1) degrees. The side-chain torsion angles in delta Phe of chi 2(1) = 1(2), chi 2(2,1) = 7(2) and chi 2(2,2) = 177(1) degrees indicate that the delta Phe residue is essentially planar. In valyl residue the two side-chain torsion angles are chi 1(1) = -65(1) and chi 1(2) = 177(1), whereas the torsion angles in Ile are chi 3(1,1) = 72(2), chi 3(1,2) = -159(2), chi 3(2) = 150(2) degrees. This is the first peptide which does not adopt a folded conformation for a sequence with a delta Phe at the (i + 2) position. The molecular packing in the crystals is stabilized by several hydrogen bonds: N1-H1-...O1 = 2.77(1) A, N2-H2...O1' = 2.95(1) A, N3-H3...O2 = 2.85(1) A and a possible weak interaction N2-H2...O2' = 3.29(1) A within the columns of molecules along the c-axis and van der Waals forces between the columns.