Incorporation of Trifluoromethylated Proline and Surrogates into Peptides: Application to the Synthesis of Fluorinated Analogues of the Neuroprotective Glycine-Proline-Glutamate (GPE) Tripeptide.
The incorporation into a peptide chain of highly hindered and weakly nucleophilic trifluoromethylated prolines, pseudoprolines and oxazolidines has been achieved. As an application, the synthesis of a new class of fluorinated analogues of the neuroprotective tripeptide glycine-proline-glutamate (GPE) is reported. These analogues have been elaborated from a panel of five-membered ring trifluoromethylated amino acids (Tfm-AAs) through the coupling reaction with a glutamate residue at the C-terminus and a glycine at the N-terminus. Although the peptide coupling reaction at the C-terminal position of the fluorinated amino acid was conveniently performed under standard conditions, the very challenging coupling reaction at the highly deactivated N-terminal position proved to be much more problematic. A methodological study was needed to identify suitable reaction conditions for this difficult peptide coupling.
Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
Julien
J
Simon
Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
Julien
J
Pytkowicz
Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
Nathalie
N
Lensen
Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
Grégory
G
Chaume
Laboratoire de Chimie Biologique (LCB), Université de Cergy-Pontoise , EA 4505, 5 Mail Gay-Lussac, 95000 Cergy-Pontoise, France.
Thierry
T
Brigaud
D005459:Fluorides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D018696:Neuroprotective Agents; D009842:Oligopeptides; D011392:Proline; D005459:Fluorides; C062053:glycyl-prolyl-glutamic acid