Glycopeptide        dendrimers: tuning carbohydrate–lectin interactions with amino acids

Ronan Euzen; Jean-Louis Reymond

doi:10.1039/C0MB00177E

Glycopeptide dendrimers: tuning carbohydrate–lectin interactions with amino acids†

Ronan Euzen*^a and Jean-Louis Reymond*^b

* Corresponding authors

^a Technicians Training Laboratory, Institute of Chemical Sciences and Engineering (ISIC-GE), Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland
E-mail: ronan.euzen@epfl.ch
Fax: +41 21 693 35 50
Tel: +41 21 693 53 93

^b Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland
E-mail: jean-louis.reymond@ioc.unibe.ch
Fax: +41 31 631 80 57
Tel: +41 31 631 43 25

Abstract

Glycodendrimers, such as glycoclusters and glycopolymers, are known to be very useful molecules to probe carbohydrate–lectin interactions. Herein, new second generation glycopeptide dendrimers (G2a–f) presenting a L-lysine-based (Lys) tetraantennary scaffold, four external thiomannosyl residues and, in the case of compounds G2b–f, four copies of a variable amino acid (X¹) were synthesized and used as Concanavalin A (Con A) inhibitors. An increased-sensitivity Enzyme-Linked Lectin Assay (ELLA) was also developed to evaluate precisely the relative strength of the glycodendrimer–lectin interactions. Glycopeptide dendrimer G2e, for which L-tyrosine (Tyr) was used as a variable amino acid, led to optimal inhibition properties (IC₅₀ = 52 μM). Additionally, glycopeptide dendrimers G2g–k built on a scaffold displaying four external Tyr and more internally, four copies of a variable amino acid (X²) were synthesized and involved in the mentioned ELLA. Even if no strong improvement was observed, such structural modulations could also modify the inhibition properties of glycopeptide dendrimers. Finally, mono-, di- and octavalent analogs of G2e, noticed, respectively, G0, G1 and G3, were produced and assayed. Multivalency then appeared as a key feature since inhibition properties of these glycoconjuguates increased with the number of carbohydrate moieties and a relatively strong cluster effect was obtained for the octavalent derivative G3 (IC₅₀ = 2.9 μM).

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Article information

DOI: https://doi.org/10.1039/C0MB00177E
Article type: Paper
Submitted: 25 Aug 2010
Accepted: 28 Sep 2010
First published: 01 Nov 2010

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Mol. BioSyst., 2011,7, 411-421

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Glycopeptide dendrimers: tuning carbohydrate–lectin interactions with amino acids

R. Euzen and J. Reymond, Mol. BioSyst., 2011, 7, 411 DOI: 10.1039/C0MB00177E

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Molecular BioSystems