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

Boris Aillard, Jeremy Dunbar Kilburn, Jeremy P. Blaydes, Graham J. Tizzard, Stuart Findlow, Joern M. Werner, Sally Bloodworth*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    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 H-1 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 H-1-N-15 HSQC NMR titration experiments.

    Original languageEnglish
    Pages (from-to)4562-4569
    Number of pages8
    JournalOrganic & Biomolecular Chemistry
    Volume13
    Issue number15
    Early online date10 Mar 2015
    DOIs
    Publication statusPublished - 21 Apr 2015

    Keywords

    • POLYPROLINE-II
    • SH3 DOMAINS
    • STEREOSELECTIVE-SYNTHESIS
    • CIRCULAR-DICHROISM
    • PEPTIDE MIMICS
    • RICH PEPTIDES
    • AMINO-ACIDS
    • PPII HELIX
    • PSEUDOPEPTIDE FOLDAMERS
    • DOPAMINE-D-2 RECEPTOR

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