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

Authors

  • Benedetto Di Blasio,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Michele Saviano,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Valerio Del Duca,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Giuseppina De Simone,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Filomena Rossi,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Carlo Pedone,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Ettore Benedetti,

    1. Biocrystallography Research Centre, CNR and Department of Chemistry University of Napoli “Federico II” Via Mezzocannone 480134 Napoli, Italy
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  • Gian Paolo Lorenzi

    1. Polymer Institute, ETH Centre, Zurich, Switzerland
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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-alle-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 R factors 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 ϕ and ψ torsion angles cosrresponding 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 super-imposable [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 isoconfiguralional side chains of the Ile or allo-Ile residues are (gt) t and (tg+) tfor the L-Ile and the D-allo-Ile moieties, respectively. In all cases, these conformations correspond to the more populated conformers of β-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. © 1995 John Wiley & Sons, Inc.

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