Carbosilane glycodendrimers

Abstract

Glycodendrimers fascinate both carbohydrate chemists and biologists because of their ability to recognize lectins and enhance carbohydrate-protein interactions. These characteristics make glycodendrimers a valuable tool in glycoscience and chemical biology. Many glycodendrimers have been described to date; this tutorial review focuses specifically on carbosilane glycodendrimers. We present methodologies for synthesizing parent carbosilane dendrimers and describe their use in biological assays. We also describe representative functionalizations of parent carbosilane dendrimers at terminal positions which are necessary for chemical ligation with carbohydrate ligands. This is followed by a description of all coupling reactions between carbohydrate and carbosilane dendrimer functionalities used in the synthesis of carbosilane glycodendrimers. The major emphasis of this review is the use of carbosilane glycodendrimers as medical agents against Shiga toxins, dengue viruses, relapsing fever Borrelia, and hemagglutinin and neuraminidase of influenza viruses, as well as on the relationship between dendrimer structure and these biological activities. The last two sections introduce recent attempts to use carbosilane glycodendrimers as new versatile and widely-applicable lectin sensors, and the use of carbosilane glycodendrimers as a novel drug carrier in an active targeting drug delivery system. This review article will be of interest to scientists in the areas of organic chemistry, chemical biology, carbohydrate chemistry, heteroatom chemistry, and organosilicon chemistry.

Fullerene‐sp2‐Iminosugar Balls as Multimodal Ligands for Lectins and Glycosidases: A Mechanistic Hypothesis for the Inhibitory Multivalent Effect

“…General procedure: The general procedure for the preparation of spacerarmed 5,6-oxomethylidenenojirimycin (1N-ONJ) and 5,6-oxomethylidenemannojirimycin (1N-OMJ) derivatives (17)(18)(19)(20) is as follows. A solution www.chemeurj.org of 5,6-oxomethylidenenojirimycin (15) or 5,6-oxomethylidenemannojirimycin (16; 1.72 mmol) and N-Boc-1,6-diaminohexane (578 mL, 2.58 mmol) or N-Boc-1,9-diaminononane (667 mg, 2.58 mmol) in MeOH (7.2 mL) was stirred, under Ar atmosphere, at 65 8C for 24-48 h. The solvent was removed under reduced pressure, and the resulting residue was purified by column chromatography using the eluent indicated in each case.…”

“…Thus, many synthetic polyconjugates with various copies of an identical individual sugar recognition motif onto molecular, dendritic, polymeric, selfassembled or nanometric scaffolds have been developed aimed at mimicking and matching the arrangement of complementary lectin receptors in their natural mode of affinity enhancement. [13][14][15][16][17][18][19][20][21] The design of glycosidase inhibitors has instead been focused on monovalent glycomimetics with a resemblance to the natural substrate or to the corresponding transition state. [22][23][24] In contrast to most lectins, glycosidases may appear to be unpromising targets for multivalent binding because the active site, which is normally unique, is generally buried at the interior of the protein and not very accessible, preventing quelation and cross-linking phenomena and making sliding and rebinding of multitopic ligands improbable.…”

Functional aqueous assemblies of linear‐dendron hybrids

“…Glycopolymers with various architectures can be self‐assembled to generate assemblies such as micelles or vesicles . Glycodendrimers have also been extensively explored . However, carbohydrates have only recently been incorporated into LD hybrids.…”

Biological Evaluation of Multivalent-Type N-Acetyl-D-Glucosamine (GlcNAc) Conjugates for Wheat Germ Agglutinin (WGA) by the Surface Plasmon Resonance (SPR) Method

“…Enzyme-linked lectin assay (ELLA) with WGA has enabled the identification of tetra-, penta-, and hexavalent glycocluster exhibiting higher binding affinity than the monomeric GlcNAc control [15]. On the basis of structural data and recent progress made in the understanding of multivalent effects, a large variety of synthetic glycoclusters based on peptide dendrimers [16], carbosilanes [17], and nanostructures [18] have been developed as ligands for studying biologically relevant targets or providing compounds with anti-pathogenic and anti-tumoral properties.…”