Design of peptides with branched β-carbon dehydro-residues: syntheses, crystal structures and molecular conformations of two peptides, (I) N-Carbobenzoxy-ΔVal-Ala-Leu-OCH₃ and (II)N-Carbobenzoxy-Δ Ile-Ala-Leu-OCH₃

Abstract

Highly specific structures can be designed by inserting dehydro-residues into peptide sequences. The conformational preferences of branched β-carbon residues are known to be different from other residues. As an implication it was expected that the branched β-carbon dehydro-residues would also induce different conformations when substituted in peptides. So far, the design of peptides with branched β-carbon dehydro-residues at (i + 1) position has not been reported. It may be recalled that the nonbranched β -carbon residues induced β-turn II conformation when placed at (i + 2) position while branched β-carbon residues induced β-turn III conformation. However, the conformation of a peptide with a nonbranched β-carbon residue when placed at (i + 1) position was not found to be unique as it depended on the stereochemical nature of its neighbouring residues. Therefore, in order to induce predictably unique structures with dehydro-residues at (i + 1) position, we have introduced branched β-carbon dehydro-residues instead of nonbranched β-carbon residues and synthesized two peptides: (I) N-Carbobenzoxy-ΔVal-Ala-Leu-OCH₃ and (II) N-Carbobenzoxy-ΔIle-Ala-Leu-OCH₃ with ΔVal and ΔIle, respectively. The crystal structures of peptides (I) and (II) have been determined and refined to R-factors of 0.065 and 0.063, respectively. The structures of both peptides were essentially similar. Both peptides adopted type II β-turn conformations with torsion angles; (I):Φ₁ = -38.7 (4)°, Ψ₁ = 126.0 (3)°; Φ₂ = 91.6 (3)°, Ψ₂ = -9.5 (4)° and (II): Φ₁ = -37.0 (6)°, Ψ₁ = 123.6 (4)°, Φ₂ = 93.4 (4), Ψ₂ = -11.0(4)° respectively. Both peptide structures were stabilized by intramolecular 4→1 hydrogen bonds. The molecular packing in both crystal structures were stabilized in each by two identical hydrogen bonds N₁...O₁' (-x, y + 1/2, -z) and N₂...O₂' (-x + 1, y + 1/2, -z) and van der Waals interactions.