Effects of branched β-carbon dehydro-residues on peptide conformations: syntheses, crystal structures and molecular conformations of two tetrapeptides: (a) N-(benzyloxycarbonyl)-ΔVal-Leu-ΔPhe-Leu-OCH₃ and (b) N-(benzyloxycarbonyl)-ΔIle-Ala-ΔPhe-Ala-OCH₃

Abstract

The roles of branched β-carbon dehydro-residues in the design of peptide conformations have not been systematically explored so far. In order to determine the effects of branched β-carbon dehydro-residues on the peptide conformations, two N-protected tetrapeptides containing new combinations of ΔVal and ΔPhe in (a) N-(benzyloxycarbonyl)-ΔVal-Leu-ΔPhe-Leu-OCH₃ and ΔIle and ΔPhe in (b) N-(benzyloxycarbonyl)-ΔIle-Ala-ΔPhe-Ala-OCH₃ were synthesized by solution procedure. The crystal structures of these peptides were determined by X-ray diffraction methods. Single crystals of both peptides were grown by slow evaporation method from their solutions in acetone-water mixtures (80 : 20) at 25°C. The crystals of these peptides belong to the orthorhombic space group P2₁2₁2₁ with cell dimensions of a = 12.342(1) Å, b = 15.659(1) Å, c = 18.970(1) Å for peptide (a) and a = 8.093(1) Å, b = 15.791(1) Å, c = 23.816(1) Å for peptide (b) having Z = 4 in the unit cells of both peptides. The structures were refined by full-matrix least-squares procedure to R-factors of 0.076 and 0.052 respectively. Both peptides adopt the right-handed 3₁₀-helical conformations stabilized by two intramolecular (i + 3→i) hydrogen bonds between the CO of N-terminal benzyloxycarbonyl (Cbz) group and the NH of residue at position 3, and between the CO of residue at position 1 and NH of the residue at position 4. The two consecutive 10-membered rings formed by the hydrogen bonds have dihedral angles corresponding to the standard values for type III β-turns. ΔVal and ΔIle in peptides (a) and (b) respectively are located at the (i + 1) position of the first β-turn while ΔPhe is located at the (i + 2) position of the second β-turn. In the crystals, the molecules are linked head to tail by intermolecular hydrogen bonds to form long helical chains. The axes of helices are parallel to the b-axes while the neighbouring helices run in the opposite directions. The crystal packings are further stabilized by van der Waals forces between the columns of molecular packings.