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Updated: Jul 15, 2025

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
Published on: February 6, 2020
Supramolecular multivalency effects enhance imine formation in aqueous medium allowing for dynamic modification of
Ferran Esteve1, Fidan Rahmatova1, Jean-Marie Lehn1
1Laboratoire de Chimie Supramoléculaire, Institut de Science et d'Ingénierie Supramoléculaires (ISIS), Université de Strasbourg 8 allée Gaspard Monge 67000 Strasbourg France estevefranch@unistra.fr lehn@unistra.fr.
Abstract:
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 (i.e., acylhydrazide).
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