Design of peptides with α, β-dehydro-residues: synthesis and crystal structure of a tripeptide N-benzyloxycarbonyl-ΔVal-ΔPhe- l-Ala-OCH 3

Abstract

In order to develop the design rules for producing specific conformations of peptides with α, β-dehydro-residues a peptide Cbz-ΔVal-ΔPhe-Ala-OCH 3 was synthesized in solution phase. The crystal structure has been determined by X-ray diffraction method. The structure was refined to an R-value of 0.050. The peptide adopts a type I β-turn conformation with backbone torsion angles of two corner residues, ϕ 1=−53.9(6)°, ψ 1=−33.0(6)°, ϕ 2=−73.7(5)° and ψ 2=−12.2(6)°. The conformation is stabilized by an intramolecular 4→1 hydrogen bond involving NH of Ala residue as a donor and carbonyl oxygen atom of Cbz group as an acceptor. The torsion angles, χ 1 1 , 1 = 172.8 ( 6 ) and χ 1 1 , 2 = − 6.9 ( 9 ) of ΔVal residue indicate that its side chain is planar while the torsion angles, χ 2 1 = − 9.0 ( 9 ) , χ 2 2 , 1 = − 43.4 ( 10 ) and χ 2 2 , 2 = 130.1 ( 9 ) show that the side chain of ΔPhe deviates considerably from the planarity. This is the first sequence in which ΔVal and ΔPhe are introduced at adjacent positions and the structure reveals clearly that the side chain of ΔPhe is a relatively less rigid than that of ΔVal. The molecules are packed in columns parallel to c-axis.