Effect of lengthening of peptide backbone by insertion of chiral β-homo amino acid residues : conformational behavior of linear peptides containing alternating L-leucine and β-homo L-leucine residues

The synthesis and the solution behavior of the linear peptides containing a β-homo (β-H) leucine residue-Boc-Leu-β-HLeu-Leu-OMe, Boc-β- HLeu-Leu-β-HLeu-Leu-OMe, and Boc-Leu-β-HLeu-Leu-β-HLeu-Leu-OMeas well as the solid structure of the tripeptide, are reported. The conformational behavior of the peptides was investigated in solution by two-dimensional nmr. Our data support the existence in solution with different families of conformers in rapid interchange. The crystals of the tripeptide are orthorhombic, space group P21212, with a = 15.829(1) Å, b = 29.659(1) Å, c = 6.563(1) Å, and Z = 4. The structure has been solved by direct methods and refined to final R1 and wR2 indexes of 0.0530 and 0.1436 for 2420 reflections with I > 2σ(I). In the solid state, the tripeptide does not present intramolecular H bonds, and the peptide backbone of the two leucine residues adopts a quasi-extended conformation. For the β-HLeu residue, the backbone conformation is specified by the torsion angles φ2 = -120.9(4)°, μ2 = 56.7(4)°, ψ3 = -133.2(4)°. The side chains of the three residues assume the same conformation (g-, g-, trans), and all peptide bonds, except the urethane group at the N-terminus, are in the trans conformation. Preliminary conformational energy calculations carried out on the Ac-NH-β- HAla-NHMe underline that the conformations with μ angle equal to 180°and 60° assume lower energy with respect to the others. In addition, we found a larger conformational freedom for the ψ angle with respect to the φ angle.