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Accueil > Équipes de recherche > Molécules fluorées et peptides d’intérêt thérapeutique - FLUOPEPIT > A Cover paper

A Cover paper

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. https://doi.org/10.1039/C9OB02654A

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. http://dx.doi.org/10.1016/j.tet.2013.02.012