Conformational studies of heterochiral peptides with diastereoisomeric residues: Crystal and molecular structures of linear dipeptides derived from leucine, isoleucine, and allo‐isoleucine

Abstract

The x-ray diffraction analyses of three N- and C-terminally blocked L,D dipeptides, namely t-Boc-D-Leu-L-Leu-OMe (1), t-Boc-L-Ile-D-aIle-OMe (2), and t-Boc-D-aIle-L-Ile-OMe (3) containing enantiomeric or diastereomeric amino acid residues have been carried out. The structures were determined by direct methods and refined anisotropically to final Rf actors of 0.077, 0.058, and 0.072 for (1), (2), and (3), respectively. Peptides 1-3 all assume a similar U-shaped structure with phi and psi torsion angles corresponding to one of the possible calculated minimum energy regions (regions E and G for L residues, and F*, D* and H* for D residues). The peptide backbones of 1-3 are almost superimposable [provided that the appropriate inversion of the chiral centers of (2) is made]. Side-chain conformations of Leu residues in peptide (1) are g- (tg-) for the L-Leu residue and the mirrored g+ (tg+) for the D-Leu residue; however, in peptides (2) and (3) the conformations of the isoconfigurational side chains of the Ile or allo-Ile residues are (g-t) t and (tg+) t for the L-Ile and the D-allo-Ile moieties, respectively. In all cases, these conformations correspond to the more populated conformers of beta-branched residues statistically found in crystal structures of small peptides. The results seem to indicate that, at least in short peptides with enantiomeric or diastereoisomeric residues, the change in chirality in the main-chain atoms perturbs the backbone conformation to a lesser extent and the side chain conformation to a greater extent.

Intramolecular CH···O Hydrogen‐bond mediated stabilization of a Cis‐DPro imide‐bond in a stereocontrolled heterochiral model peptide

“…Besides, while main-chain torsion angles of the Thr residue in 1 are significantly extended (/ $ 2123; C T $173), the corresponding angles of the C-terminus residue in correlated peptides adopted either semi-folded (/ 5 2145 6 5; C T 5 245 6 158 in Boc- Met-Met-OMe) conformation. 38,39 However, despite gross conformational differences at the molecular level, the former correlated peptides show remarkably similar molecular self-assembly and supramolecular architecture. 38 The results clearly suggest that the overall stereochemical restrictions imposed via side-chains in peptide 1 clearly enforced the fabrication of a weak CÀ ÀH.…”

“…38,39 However, despite gross conformational differences at the molecular level, the former correlated peptides show remarkably similar molecular self-assembly and supramolecular architecture. 38 The results clearly suggest that the overall stereochemical restrictions imposed via side-chains in peptide 1 clearly enforced the fabrication of a weak CÀ ÀH. .…”

“….O¼ ¼C intramolecular hydrogen-bond. 28,32 In the past, Benedetti and coworkers 38 attempted to feature the importance of U-shaped molecular structures to produce rather predictable supramolecular self-assembly from enantiomeric and diastereomeric correlated peptides Boc-D AaaAaa-OMe, where Aaa may be a Leu, aIle, or Met residue. 38,39 Taken together, these studies tend to point out the propensity(ies) of terminally protected homochiral L,L and heterochiral D,L dipeptides for accommodating diverse biologically relevant folded-unfolded structures 40,41 and probably, their controlled supramolecular self-assembly.…”

“…28,32 In the past, Benedetti and coworkers 38 attempted to feature the importance of U-shaped molecular structures to produce rather predictable supramolecular self-assembly from enantiomeric and diastereomeric correlated peptides Boc-D AaaAaa-OMe, where Aaa may be a Leu, aIle, or Met residue. 38,39 Taken together, these studies tend to point out the propensity(ies) of terminally protected homochiral L,L and heterochiral D,L dipeptides for accommodating diverse biologically relevant folded-unfolded structures 40,41 and probably, their controlled supramolecular self-assembly. [38][39][40][41] In view of prospective implications of C b -branched residues in peptide design, we extend our exploration and describe herein the crystal molecular structure and shapespecific supramolecular self-assembly of a stereocontrolled heterochiral model peptide Boc-D Pro-Thr-OMe (1) and compare its 13 C NMR spectral characteristics with correlated model peptide Boc-D Thr-Thr-OMe (2) and the derivative Boc-Thr-OMe (3).…”

“…38,39 Taken together, these studies tend to point out the propensity(ies) of terminally protected homochiral L,L and heterochiral D,L dipeptides for accommodating diverse biologically relevant folded-unfolded structures 40,41 and probably, their controlled supramolecular self-assembly. [38][39][40][41] In view of prospective implications of C b -branched residues in peptide design, we extend our exploration and describe herein the crystal molecular structure and shapespecific supramolecular self-assembly of a stereocontrolled heterochiral model peptide Boc-D Pro-Thr-OMe (1) and compare its 13 C NMR spectral characteristics with correlated model peptide Boc-D Thr-Thr-OMe (2) and the derivative Boc-Thr-OMe (3). The latter peptides serve as control for analysing 13 C NMR spectral characteristics associated with the Thr residue.…”