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

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

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 an...

Full description

Bibliographic Details
Main Authors: Aillard, Boris (Author), Kilburn, Jeremy D. (Author), Blaydes, Jeremy P. (Author), Tizzard, Graham J. (Author), Findlow, I.Stuart C. (Author), Werner, Jörn M. (Author), Bloodworth, Sally (Author)
Format: Article
Language:English
Published: 2015-03-10.
Subjects:
Article
Online Access:Get fulltext
Description
Summary: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.

Similar Items