Synthesis of “Mixed Type” Oligosaccharide Mimetics Based on a Carbohydrate Scaffold

Abstract

In multivalent glycoligands including cluster glycosides, one type of sugar epitope is normally clustered. Such molecules have been valuable tools for investigation and inhibition of cell adhesion processes. They have, for example, served as in vitro antiadhesives in mannose‐specific bacterial adhesion. Wild‐type bacteria, however, utilize a number of different sugar epitopes for adhesion, involving bacterial lectins of different specificity. The synthesis of glycomimetics containing sugar derivatives from different sugar series is therefore of interest, with the eventual goal of providing multivalent glycoligands of a more complex type. The synthesis of novel “mixed” glycoclusters, starting from the trifunctional galactoside 10 that serves as a carbohydrate scaffold, is hence presented here. Compound 10 has three potential reactive sites, which were addressed successively. Firstly, peptide coupling with the carboxy‐functionalized mannoside 11 furnished the disaccharide mimetic 13, which in turn provided the trisaccharide mimetic 19 after peptide coupling with the amino‐functionalized fucoside 17. Finally, a pentasaccharide mimetic 23 was obtained after thiourea‐bridging with acetylated lactosyl isothiocyanate.

Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant

“…Multivalent, relatively low molecular weight constructs have been described [37][38][39][40][41][42][43] preparation of tailored neoglycoconjugates having two different synthetic carbohydrates attached to one protein carrier has not been reported. This makes conjugate D principally novel in that one of the chemically attached ligands is a synthetic, disease specific antigen and the other is a synthetic molecule specifically chosen to enhance the overall immunogenicity of the resulting construct.…”

Click Multivalent Heterogeneous Neoglycoconjugates – Modular Synthesis and Evaluation of Their Binding Affinities

“…However, in nature, a number of different sugar ligands may be essential for a biological recognition process. In spite of this, a limited number of synthetic, multivalent, heterogeneous neoglycoconjugates containing different sugar epitopes has been described to date 10–18…”

“…The reported hetero carbohydrate displays having a glycocluster,10,11 glycodendrimer,12–14 glycocyclodextrin,15 or glycopolymer16,17 architecture have been constructed by means of two different synthetic strategies for the incorporation of the different saccharide ligands: 1) by using an orthogonal protection of a polyfunctional core molecule for the successive attachment of the different sugar moieties10,11,13 or 2) by controlling the relative proportions of the carbohydrate reagents in the reaction with a homogeneous, functionalized, reactive core 12,14–17. In this last option, the heterogeneous functionalization can be performed following a sequential12,14,15 or a simultaneous16,17 conjugation pattern using pure carbohydrate reagents or mixtures of them, respectively, allowing in this way a modulation of the sugar density.…”

“…In this last option, the heterogeneous functionalization can be performed following a sequential12,14,15 or a simultaneous16,17 conjugation pattern using pure carbohydrate reagents or mixtures of them, respectively, allowing in this way a modulation of the sugar density. The covalent attachment of sugar moieties to the selected scaffolds have been performed by means of amide,10,11 thiourea,10,12,14 thioether,15 and triazole13,16,17 linkage constructed by the reaction of sugar derivatives containing amino, acid, thiocyanate, thiol, and azide groups, respectively.…”

Multivalency in heterogeneous glycoenvironments: hetero-glycoclusters, -glycopolymers and -glycoassemblies

“…21,22 In 2002, Lindhorst and co-workers proposed an approach based on the orthogonal derivatization of D-galactopyranose to attach different sugars (a-D-mannose = aMan, a-L-fucose = aFuc and b-lactose = bLact), thereby accessing novel ''mixed''-or ''hetero''-glycoclusters (e.g., 2). 23 The different coating saccharides were sequentially incorporated, after activation of amine or carboxylic acid functional groups, through amide or thiourea ligation chemistries. Amide bond formation was also privileged for the construction of the heterodivalent glycoconjugate 3, bearing a mannose trisaccharide and a monomeric mannosyl unit in separate branches (Fig.…”