Promotion of sugar–lectin recognition through the multiple sugar presentation offered by regioselectively addressable functionalized templates (RAFT): a QCM-D and SPR study

Abstract

The investigation of recognition events between carbohydrates and proteins, especially the understanding of how spatial factors and binding avidity are correlated, remains a great interest for glycobiology. In this context we have investigated by nanogravimetry (QCM-D) and surface plasmon resonance (SPR), the kinetics and thermodynamics of the interaction between concanavalin A (Con A) and various neoglycopeptide ligands of low molecular weight. Regioselectively addressable functionalized templates (RAFT) have been used as scaffolds for the design of multivalent neoglycopeptides bearing thiol or biotin functions for their anchoring on transducer surfaces. Although these multivalent neoglycopeptide ligands cannot span multiple binding sites within the same Con A protein, they have increased activities relative to their monovalent counterpart. Our results emphasize that the multivalent RAFT ligands function by clustering several lectins, which leads to enhanced affinities.

Recent progress in the field of neoglycoconjugate chemistry

“…In this way, aminooxy carbohydrates have been prepared by reaction of N-hydroxysuccimide with glycosyl chlorides (98) or N-hydroxyphthalimide with fluoride-activated sugars (99). The electrophilic carbonyl on the peptide is generated either by ozonolysis of dehydroleucine (98) or by periodate oxidation of Ser (100). Oxime ligation between these aminooxy and carbonyl components has allowed the synthesis of both linear and multivalent neoglycopeptides.…”

Recent Developments in Neoglycopeptide Synthesis

“…Dumy et al [41] used oxime formation to generate regioselectively addressable functionalized templates (RAFTs amino-oxylated lactose to produce tetravalent glycoclusters in an effort to enhance lectin binding (Scheme 11.8). This chemistry was also used for the chemoselective modification of acetalprotected dextran particles using alkoxyamine-functionalized fluorophores or an alkoxyamine-terminating poly(arginine) sequence derived from cell-penetrating peptides.…”

A Fully Solid-Phase Synthesis of Biotinylated Glycoclusters

“…Particularly, we have reported the synthesis of diverse multivalent labeled glycoclusters combined solid-phase and solution convergent strategy [18]. The binding properties of biotinylated glycoconjugates with lectins have been recently confirmed using surface plasmon resonance and nanogravimetry experiments [19] after immobilization on streptavidin-coated *Address correspondence to these authors at the Département de Chimie Moléculaire, UMR-CNRS 5250 & ICMG FR 2607, Université Joseph Fourier, F-38041 Grenoble Cedex 9, France; E-mail: olivier.renaudet@ujf-grenoble.fr; pascal.dumy@ujf-grenoble.fr surfaces. In order to improve our synthetic method by reducing the number of time-consuming purification steps, we have designed the peptidic template so that a fully supported synthesis, including the cyclization of the peptide, the topological functionalization with biotins and the chemoselective incorporation of sugars which are commonly performed in solution, can be entirely realized on solid-phase ( Fig.…”