CBL Chemical Biology Lab

Fluorinated Pseudoprolines

One of our research topics is focused on the synthesis of trifluoromethylated pseudoprolines (CF3-ΨPro), derived from serine [Ser(ΨCF3,HPro)] or cysteine [Cys(ΨCF3,HPro)], and their incorporation into peptides. The introduction of the CF3 group at the Cδ position strongly improves the chemical stability of the pseudoproline core in acidic media compare to non-fluorinated pseudoprolines. Accordingly, CF3-ΨPro behave as hydrolytically stable proline surrogates. Moreover, we have demonstrated that the incorporation of a Ser(ΨCF3,HPro) residue into a peptide chain can lower the rotational barrier of the cistrans peptide bond isomerization, enhance the cis population ratio, freeze the puckering of the oxazolidine core and tune the peptide conformation depending of the absolute configuration at the Cδ position and the solvent polarity. In the course of our studies, we developed efficient coupling reactions that allow the synthesis of several C- or N-terminal CF3-ΨPro containing dipeptides as building blocks for SPPS.

 

Incorporation of CF3−Pseudoprolines into Peptides: A Methodological Study, Chaume, G.; Simon, J.; Caupène, C.; Lensen, N.; Miclet, E.; Brigaud, T. J. Org. Chem. 2013, 78, 10144-10153.

Conformational properties of peptides incorporating a fluorinated pseudoproline residue, Chaume, G.; Feytens, D.; Chassaing, G.; Lavielle, S.; Brigaud, T.; Miclet, E. New J. Chem. 2013, 37, 1336-1342.

Local control of the cis-trans isomerization and backbone dihedral angles in peptides using trifluoromethylated pseudoprolines, Feytens, D.; Chaume, G.; Chassaing, G.; Lavielle, S.; Brigaud, T.; Byun, B. J.; Kang, Y. K.; Miclet, E. J. Phys. Chem. B 2012, 116, 4069-4079.

Synthesis of 2-Trifluoromethyl-1,3-oxazolidines as Hydrolytically Stable Pseudoprolines, Chaume, G. ; Barbeau, O. ; Lesot, P. ; Brigaud, T. J. Org. Chem. 2010, 75, 4135-4145.

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