Synthesis Of Glycoclusters Research Articles

ChemInform Abstract: Unprotected Carbohydrates as Starting Material in Chemical Synthesis: Not Just a Challenge but an Opportunity

AbstractReview: [34 refs.

Unprotected Carbohydrates as Starting Material in Chemical Synthesis: Not Just a Challenge but an Opportunity

Development of reaction sequences that utilize renewable resources, such as carbohydrates, as starting material is of topical interest. Particularly attractive are reaction protocols where unprotected mono- and oligosaccharides are applied. Herein, selected approaches for direct derivatization of unprotected carbohydrates are highlighted. Ultimately, such methodologies are also applicable for natural polysaccharides resulting in rapid development of novel functional biobased materials for future applications. 1 Introduction 2 Reacting Unprotected Carbohydrates as Aldehydes 3 Approaches for Selective Reactions Targeting the Nonanomeric Hydroxyl Groups on Unprotected Carbohydrates 4 Protecting-Group-Free Synthesis of Glycoclusters and Glycoconjugates 5 Conclusions

ChemInform Abstract: Synthesis of Octopus Glycosides: Core Molecules for the Construction of Glycoclusters and Carbohydrate-Centered Dendrimers.

Abstract Allyl α- d -glucopyranoside was perallylated to allyl 2,3,4,6-tetra-O-allyl-α- d -glucopyranoside and this was converted into an array of uniformly functionalized spacer glycosides of an “octopus” type, taking advantage of the rich chemistry of the allyl ether function. Thus, carbohydrate-derived pentaaldehydes, pentaalcohols and pentaamines with different spacer lengths were obtained by ozonolysis, reductive amination, hydroboration or photoaddition of cysteamine hydrochloride, respectively. The new octopus glycosides are useful core molecules for the synthesis of glycoclusters and for the construction of carbohydrate-centered dendrimers.

Coloring Carbohydrates: Investigation of Azulene Derivatives as Blue Protecting Groups

Coloring carbohydrate derivatives by a chromophore tag greatly facilitates all purification steps during a synthetic sequence, according to a methodology called “chromophore-supported purification” (CSP). Herein an Fmoc-analogous blue protective group for CSP is introduced, based on guaiazulene. Following a mechanistic rational, the synthesis and introduction of this new protecting group is shown, together with its removal under variable conditions and its application for the synthesis of glycoclusters of a glycopeptide and glycopeptoid type.

Synthesis of bi- and tervalent ligands of galectins, derivatives of β-lactosylamine, with the amino group in the terminal position of the spacer

A method for the synthesis of glycoclusters by N-alkylation of N-glycyl-β-lactosylamine with N-chloroacetyl derivatives of β-lactosylamine and N,N’-iminodiacetyldilactosylamine has been developed. The glycoclusters obtained with two and three lactosylamine residues with the amino group in the spacer were found to be suitable for further conjugation with carboxy-containing physiologically active compounds.

Synthesis of Glycocluster−Tumor Antigenic Peptide Conjugates for Dendritic Cell Targeting

The use of dendritic cells (DC) for the development of therapeutic cancer vaccines is attractive because of their unique ability to present tumor epitopes via the MHC class I pathway to induce cytotoxic CD8+ T lymphocyte responses. C-Type membrane lectins, DC-SIGN and the mannose receptor (MR), present on the DC surface, recognize oligosaccharides containing mannose and/or fucose and mediate sugar-specific endocytosis of synthetic oligolysine-based glycoclusters. We therefore asked whether a glycotargeting approach could be used to induce uptake and presentation of tumor antigens by DC. To this end, we designed and synthesized glycocluster conjugates containing a CD8+ epitope of the Melan-A/Mart-1 melanoma antigen. These glycocluster-Melan-A conjugates were obtained by coupling glycosynthons: oligosaccharyl-pyroglutamyl-beta-alanine derivatives containing either disaccharides, a dimannoside (Manalpha-6Man) or lactoside, or a Lewis oligosaccharide, to Melan-A 16-40 peptide comprising the 26-35 HLA-A2 restricted T cell epitope, extended with an oligolysine stretch at the C-terminal end. We showed by confocal microscopy and flow cytometry that fluorescent-labeled Melan-A glycoclusters containing either dimannoside or Lewis oligosaccharide were taken up by DC and concentrated in acidic vesicles; conversely lactoside glycopeptides were not at all taken up. Furthermore, using surface plasmon resonance, we showed that dimannoside and Lewis-Melan-A conjugates bind MR and DC-SIGN with high affinity. DC loaded with these conjugates, but not with the lactose-Melan-A conjugate, led to an efficient presentation of the Melan-A epitope eliciting a CD8+ T-lymphocyte response. These data suggest that synthetically designed glycocluster-tumor antigen conjugates may induce antigen cross-presentation by DC and represent a promising tool for the development of tumor vaccines.