Design of peptides with αβ-dehydro residues: synthesis, crystal structure and molecular conformation of N-Boc-L-Ile-ΔPhe-L-Trp-OCH3

Vijayaraghavan, R. ; Kumar, P. ; Dey, S. ; Singh, T. P. (1998) Design of peptides with αβ-dehydro residues: synthesis, crystal structure and molecular conformation of N-Boc-L-Ile-ΔPhe-L-Trp-OCH3 The Journal of Peptide Research, 52 (2). pp. 89-94. ISSN 1397-002X

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Official URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1399-...

Related URL: http://dx.doi.org/10.1111/j.1399-3011.1998.tb01362.x

Abstract

The dehydro-peptide Boc-L-Ile-ΔPhe-L-Trp-OCH3 was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P212121 with a = 10.777(2), b= 11.224(2), c= 26.627(10) Å. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [l≥ 2σ(l)].The peptide failed to adopt a folded conformation with backbone torsion angles: φ1, = 90.8(8)°, ψ1= -151.6(6)°, φ2= 89.0(8)°, ψ2= 15.9(9)°, φ3= 165.7(7)°, ψT3= -166.0(7)°. A general rule derived from earlier studies indicates that a three-peptide unit sequence with a ΔPhe at the (i+ 2) position adopts a β-turn II conformation. Because the branched β-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the ΔPhe residue differently to generate a unique set of conformations in such peptides. The presence of β-branched residues simultaneously at both (i+ 1) and (i+ 3) positions induces unfolded conformations in tetrapeptides, but a β-branched residue substituted only at (i+ 3) positron can not prevent the formation of a folded β-turn II conformation. On the other hand, the present structure shows that a β-branched residue substituted at the (i+ 1) position prevents the formation of a β-turn II conformation. These observations indicate that a β-branched residue at the (i+ 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i+ 3) position. This may be because of the trans disposition of the planar ΔPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N2-H2...O2 (-x,y-1/2, -z+ 3/2) and Nε13-Hε13...O1(-x,y -1/2, -z+ 3/2) hydrogen bonds.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Conformation; Crystal Structure; Dehydro-Phe; Peptide; Unfolded Conformation
ID Code:49117
Deposited On:18 Jul 2011 14:19
Last Modified:18 Jul 2011 14:19

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