Supramolecular multivalency effects enhance imine formation in aqueous medium allowing for dynamic modification of enzymatic activity.
Fiche publication
Date publication
septembre 2023
Journal
Chemical science
Auteurs
Membres identifiés du Cancéropôle Est :
Pr LEHN Jean-Marie
Tous les auteurs :
Esteve F, Rahmatova F, Lehn JM
Lien Pubmed
Résumé
Imine formation under physiological conditions represents a challenging reaction due to the strong propensity of aldimines to be hydrolyzed. Herein we disclose the remarkable effect of supramolecular multivalency on increasing imine stability. A family of reactive aldehydes was synthesized bearing supramolecularly-active sites within their structure. The imine formation activity for such aldehydes was evaluated and compared with model aldehydes. The reaction of the best-performing species - containing two carboxylate groups-with a set of amines showed a significant decrease in imine yields as the degree of supramolecular multivalency between sidechains decreased. The reversible conjugation of amino acid derivatives and small peptides was also assayed, with excellent selectivities for the imine formation at the Nα position even in substrates containing competing sites. Preliminary results on protein bioconjugation revealed that a model enzyme could be dynamically inhibited upon reaction with the aldehyde, with its native activity being recovered by displacing the imine bonds with a suitable chemical effector (, acylhydrazide).
Référence
Chem Sci. 2023 09 27;14(37):10249-10257