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 language | English |
---|---|
Pages (from-to) | 4562-4569 |
Number of pages | 8 |
Journal | Organic & Biomolecular Chemistry |
Volume | 13 |
Issue number | 15 |
Early online date | 10 Mar 2015 |
DOIs | |
Publication status | Published - 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