Conformational characteristics of peptides containing α,β‐dehydroamino acid residues

Abstract

The structural preferences of synthetic peptides containing α,β‐dehydroamino acid residues, as determined by theoretical studies, x‐ray diffraction analyses, and spectroscopic studies, are reviewed. The role of ΔZ Phe residues in stabilizing type II β‐turn structures in small peptides and in nucleating helical structure in longer peptides is exemplified by several crystal as well as solution structural studies. From the few studies reported so far it appears that ΔZ Leu influences the peptide backbone, much like the ΔZ Phe residue, whereas ΔAla prefers the extended conformation, suggesting that the nature of β substituents might influence the conformation restriction behavior of the dehydroresidues. Conformational studies on synthetic peptides containing ΔE, ΔZ Abu, and ΔVal have also been described. © 1996 John Wiley & Sons, Inc.

Structural and conformational properties of (Z)-?-(1-naphthyl)- dehydroalanine residue

“…Here it has been pointed out that the types of amino acid residues (Y) in a -Y-⌬ Z Phe-or -Y-⌬ Z Leu-segment significantly influence (, ) torsion angles in the peptide backbone. 37 The segments of Y ϭ Gly with no sidechain group and of Y ϭ Ala with the smallest side chain induced a structure close to an ideal type II ␤-turn. On the other hand, in Y ϭ Phe with a bulky side chain, the segment led to a distorted type II ␤-turn due to enhanced steric hindrance between the phenyl group of Phe and side chain of dehydroresidues (⌬ Z Phe and ⌬ Z Leu).…”

“…The two peptide bonds around the ⌬ Z Nap residue took trans conformations characterized by 1 ϭ 178.1(5)°and 2 ϭ 173.4(5)°, likewise in other dehydroresidues. 37 In the side chain of the ⌬ Z Nap residue, the 2 1 and 2 1 Ј angles were 6(1)°and 177.6(6)°, meaning the stereochemistry about the C ␣ AC ␤ double bond is essentially planar. This is consistent with the nature of a sp 2 hybrid carbon on C ␣ , as mentioned in the structural property.…”

“…Therefore, conformational properties of ⌬ Z Nap residues can be characterized by type II ␤-turn and 3 10 -helix, which have been found in many ⌬ Z Phe-containing peptides. 37 In ␤-substituted ␣,␤-dehydroalanine, the sidechain freedom would be smaller than those for naturally occurring residues such as Phe, Asp, Glu, and Lys, because the variable side-chain dihedral angle is regarded as single due to prohibited rotation about the C ␣ AC ␤ double bond. Thus, ␤-substituted dehydroalanine will be expected to be a unique residue for regularly and spatially arranging ␤ substituent(s) along the peptide backbone.…”

A helical arrangement of ?-substituents of dehydropeptides: Synthesis and conformational study of sequential nona- and dodecapeptides possessing (Z)-?-(1-naphthyl)dehydroalanine residues

“…Also, 3 10 -or ␣-helical conformations give the proximity of backbone protons between non-neighboring residues in the sequence 55 ; the ␣N(i,iϩ2) and ␣N(i,iϩ3) distances are 3.8 and 3.3 Å for a standard 3 10 -helix, and 4.4 and 3.4 Å for a standard ␣-helix. The corresponding NOEs were observed with a moderate intensity-e.g., for peptide n ϭ 4, ␣N(1,3), ␣N(1,4), ␣N (3,5), ␣N (3,6), ␣N(4,6), ␣N (6,8), ␣N (9,11), and ␣N (10,12). Therefore, peptides n ϭ 3 and 4 form a 3 10 -or ␣-helical conformation in solution.…”

N-ACETYL-α,β-DEHYDROAMINO ACIDN'-METHYLAMIDES AND N',N'-DIMETHYLAMIDES

“…As a consequence, these amino acids provide conformational constraint to the peptide backbone and restrict the orientation of the side chain P-substituent(s), and hence generate often specific peptide secondary structures (for recent reviews on a$-dehydropeptides, see Ref. [1][2][3]. However, relatively little effort has been directed to explore the stereoelectronic interactions of bond Ca=Cp with neighboring peptide bonds."…”