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Journal of Chemical Crystallography

, Volume 40, Issue 7, pp 608–615 | Cite as

Refined Crystal Structure and Absolute Configuration of the Di-amino Acid Peptide Cyclo(l-Aspartyl-l-Aspartyl): Comparison with the DFT Calculated Structure

  • Rex A. Palmer
  • Brian S. Potter
  • Andrew P. Mendham
  • Trevor J. Dines
  • Babur Z. Chowdhry
Original Paper

Abstract

The X-ray crystal structure of the di-amino acid peptide cyclo(l-Asp-l-Asp), C6H10N2O4, has been re-determined at 20 °C using CuKα radiation, λ = 1.54180 Å. The crystals are triclinic P1 with unit cell dimensions a = 5.0829(3), b = 5.0285(4), c = 18.8765(10) Å, α = 88.95(2)°, β = 83.72(2)°, γ = 74.79(2)°, unit cell volume 462.75(5) Å3, and Z = 2 independent molecules A and B per asymmetric unit. Final R indices [I > 2sigma(I)] are R1 = 0.0492, wR2 = 0.1039 for 2,540 independent reflections; R1 = 0.0686 and wR2 = 0.1112 for all 3,193 data; Goodness of Fit, S = 0.979, and the Flack x parameter = 0.1(3). In both molecules the overall shape of the diketopiperazine (DKP) ring displays an almost identical slightly distorted boat conformation with pseudo symmetry C2v (mm2). The two side chains of the cyclic peptide on opposite sides of both molecules differ in their conformations, one side being extended and the other coiled. The coiled chains are located away from the DKP ring plane while the extended chains lie approximately parallel to it. The crystal packing employs two strong hydrogen bonds, which traverse the entire crystal via translational repeats. The geometry of cyclo(l-Asp-l-Asp) derived from Ab initio calculations is compared with those of molecules A and B derived from the X-ray structure reported here. In this calculated model the DKP ring is in a pseudo twist boat conformation; both side chains are extended and lie approximately parallel to the DKP ring face as opposed to molecules A and B in the X-ray structure in each of which one side chain is approximately parallel and the other is folded away from the DKP ring face.

Graphical Abstract

Cyclic di-amino acid peptides are amongst the “simplest” peptide derivatives commonly found in nature and continue to be of long-standing interdisciplinary scientific interest with respect to potential pharmaceutical applications. Cyclo(l-Asp-l-Asp) is an example of a cyclic di-amino acid peptide, which has a six membered ring, and the amide linkage adopts a cis conformation. In contrast linear (l-Asp-l-Asp) is zwitterionic and has a single amide function which adopts the trans conformation. The synthesis and an X-ray structure of cyclo(l-Asp-l-Asp) have previously been reported, the latter being assigned the wrong absolute configuration. For the purposes of the present study, requiring precise molecular geometry, it was decided to carry out a re-determination of the crystal structure using a more complete measured set of independent intensities (94% against 36%) and correspondingly improved data/parameter ratio (3193/326 against 1215/369).

Keywords

Cyclic dipeptide Crystal structure Absolute configuration Ring geometry 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.School of Crystallography, Birkbeck CollegeUniversity of LondonLondonUK
  2. 2.Division of Electronic Engineering & PhysicsUniversity of DundeeDundeeUK
  3. 3.School of ScienceUniversity of Greenwich at MedwayKentUK

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