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A Cover paper

While peptides have demonstrated increasing interest as drugs, one major current issue is the design of small peptide analogues able to adopt preferential conformations, while possessing side chains similar to natural peptides in order to preserve their unique selectivity. We report in this article the synthesis and structural data based on experimental NMR conformational studies of peptides containing consecutive aza-amino acids. We demonstrate that a β-turn folding is induced by the introduction of one or two lateral chains on the diaza-peptide unit and that this folding is stable in aqueous media. This result is of particular importance for the design of peptidomimetics of biological interest. This work will be useful to investigate the ability of longer peptides containing these diaza-amino acids units to target protein-protein interactions (PPIs) involving turn or helical secondary structures or to stabilize the helical conformation of intrinsically disordered proteins (IDPs). PPIs and IDPs represent two of the most challenging drug discovery targets nowadays.

A major current issue in medicinal chemistry is the design of small peptide analogues resistant to proteolysis and able to adopt preferential conformations, while preserving the selectivity and efficiency of natural peptides. Whereas the introduction of one aza-Gly in peptides has proven numerous biological and structural interest, the conformational effect of sequential aza-Gly or azaamino acids bearing side chains has not been investigated. In this work, experimental NMR and X-ray data together with in silico conformational studies reveal that the introduction of two consecutive aza-amino acids in pseudotripeptides induces the formation of stable hydrogen-bonded β-turn structures. Notably, this stabilization effect relies on the presence of side chains on aza-amino acids, as more flexible conformations are observed with aza-Gly residues. Remarkably, a longer aza/aza/α/aza/aza/α pseudohexapeptide containing substituted aza-amino acids adopts repeated β-turns conformations which interconvert with a fully helical structure mimicking a 310 helix.

Introducing sequential aza-amino acids units induces repeated β-turns and helical conformations in peptides
Nicolo Tonali, Isabelle Correia, Jacopo Lesma, Guillaume Bernadat, Sandrine Ongeri and Olivier Lequin.
Org. Biomol. Chem 2020, 18, 3452.

Novel regioisomers of trifluoromethylated cyclopropanes have been synthesized by Michael addition and nucleophilic cyclization process. The reaction was carried out with the trifluoromethylcrotonate and nucleophilic reagents. Fluorinated cyclopropanes were obtained with good to excellent diastereoselectivities. Furthermore, interesting constrained building blocks have emerged from this methodology.

Access to novel amino trifluoromethyl cyclopropane carboxylic acid derivatives.
Massaba Keita, Rocco De Bona, Mickael Dos Santos, Olivier Lequin, Sandrine Ongeri, Thierry Milcent, Benoit Crousse.
Tetrahedron 2013 69 (15), 3308.