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Synthesis and evaluation of a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane scaffold as a mimic of Xaa-trans-Pro in poly-l-proline type II helix conformation

DOI: 10.1039/C5OB00180C DOI Help

Authors: Boris Aillard (University of Southampton) , Jeremy D. Kilburn (University of London) , Jeremy P. Blaydes (University of Southampton) , Graham Tizzard (University of Southampton) , Stuart Findlow (University of Southampton) , Joern Werner (University of Southampton) , Sally Bloodworth (University of Southampton)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Organic & Biomolecular Chemistry , VOL 13 (15) , PAGES 4562-4569

State: Published (Approved)
Published: March 2015
Diamond Proposal Number(s): 8521

Abstract: We describe the development of a small-molecule mimic of Xaa-trans-Pro dipeptide in poly-L-proline type II helix conformation, based upon a (3R,6S,9S)-2-oxo-1-azabicyclo[4.3.0]nonane core structure. Stereoselective synthesis of the mimic from L-pyroglutamic acid is achieved in twelve linear steps and 9.9% yield. Configurational and conformational analyses are conducted using a combination of 1H NMR spectroscopy, X-ray crystallography and circular dichroism spectroscopy; and evaluation of the mimic as a promising surrogate dipeptide, in a protein–protein interaction between the SH3 domain of human Fyn kinase (Fyn SH3) and peptidomimetics of its biological ligand, are conducted by 1H-15N HSQC NMR titration experiments.

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 25/03/2015 10:16

Discipline Tags:

Biochemistry Chemistry Life Sciences & Biotech

Technical Tags:

Diffraction Single Crystal X-ray Diffraction (SXRD)