Design of Peptides with β-Carbon Dehydroresidues: Syntheses, Crystal Structures and Molecular Conformations of Two Peptides, (I) N‐Carbobenzoxy‐ΔVal‐Ala‐Leu‐OCH3 and (II) N‐Carbobenzoxy‐ΔIle‐Ala‐Leu‐OCH3

Document Type

Article

Publication Date

2003

Department

Chemistry and Biochemistry

School

Mathematics and Natural Sciences

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.

Publication Title

Journal of Peptide Research

Volume

62

Issue

2

First Page

63

Last Page

69

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