Design of Peptides With αβ‐Dehydro Residues: Synthesis, Crystal Structure and Molecular Conformation of N‐Boc‐L‐Ile‐ΔPhe‐L‐Trp‐OCH₃

Authors

Vijayaraghavan Rangachari, University of Southern MississippiFollow
Pravindra Kumar, All India Institute of Medical SciencesFollow
Sharmistha Dey, All India Institute of Medical Sciences
Tej P. Singh, All India Institute of Medical SciencesFollow

Document Type

Article

Publication Date

1998

Department

Chemistry and Biochemistry

School

Mathematics and Natural Sciences

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)°, ψ^T₃= ‐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 N^ε1₃‐H^ε1₃…O₁(‐x,y ‐1/2, ‐z+ 3/2) hydrogen bonds.

Publication Title

Journal of Peptide Research

Volume

52

Issue

2

First Page

89

Last Page

94

Recommended Citation

Rangachari, V., 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. Journal of Peptide Research, 52(2), 89-94.
Available at: https://aquila.usm.edu/fac_pubs/7545