Effect of lengthening of peptide backbone by insertion of chiral beta-homoamino acid residues: Conformational behavior of linear peptides containingalternating L-leucine and beta-homo L-leucine residues

The synthesis and the solution behavior of the linear peptides containing a beta-homo (beta-H) leucine residue-Boc-Leu-beta-HLeu-OMe, Boc-beta-HLeu-Le u-beta-HLeu-Leu-OMe, and Boc-Leu-beta-HLeu-Leu-beta-HLeu-Leu-OMe-as well as the solid structure of the tripeptide, are reported The conformational beh avior of the peptides was investigated in solution by two-dimensional nmr. Our data support the existence in solution with different families of confo rmers in rapid interchange. The crystals of the tripeptide are orthorhombic , space group P2(1)2(1)2(1) with a = 15.829(1) Angstrom, b = 29,659(1) Angs trom, c = 6.563(1) Angstrom, and Z = 4. The structure has been solved by di rect methods and refined to final R1 and wR2 indexes of 0.0530 and 0.1436 f or 2420 reflections with I > 2 sigma(I). In the solid state, the tripeptide does nor present intramolecular H bonds, and the peptide backbone of the t wo leucine residues adapts a quasi-extended conformation. For the beta-HLeu residue, the backbone conformation is specified by the torsion angles sigm a(2) = -120.9(4)degrees, mu(2) = 56.7(4)degrees, psi(3) = -133.2(4)degrees. 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-ter minus, are in the trans conformation. Preliminary conformational energy cal culations carried out on the Ac-NH-beta-HAla-NHMe underline that the confor mations with mu angle equal to 180 degrees and 60 degrees assume lower ener gy with respect to the others. In addition, we found a larger conformationa l freedom for the psi angle with respect to the phi angle. (C) 2000 John Wi ley & Sons, Inc.