Construction of Multivalent Homo- and Heterofunctional ABO Blood Group Glycoconjugates Using a Trifunctional Linker Strategy.

The design and synthesis of multivalent ligands displaying complex oligosaccharides is necessary for the development of therapeutics, diagnostics, and research tools. Here, we report an efficient conjugation strategy to prepare complex glycoconjugates with 4 copies of 1 or 2 separate glycan epitopes, providing 4-8 carbohydrate residues on a tetravalent poly(ethylene glycol) scaffold. This strategy provides complex glycoconjugates that approach the size of glycoproteins (15-18 kDa) while remaining well-defined.

Epitope mapping of histo blood group antigens bound to norovirus VLPs using STD NMR experiments reveals fine details of molecular recognition.

Attachment of human noroviruses to histo blood group antigens (HBGAs) is thought to be critical for the infection process. Therefore, we have determined binding epitopes of synthetic type 1 to 6 blood group A- and B-tetrasaccharides binding to GII.4 human Norovirus virus like particles (VLPs) using STD NMR experiments.

Conjugation of A and B Blood Group Structures to Silica Microparticles for the Detection of Antigen-Specific B Cells.

Silica microparticles were functionalized with A and B blood group carbohydrate antigens (A type I, A type II, B type I, and B type II) to enable the detection and monitoring of ABO antigen-specific B cells. Microparticles were prepared via the Stöber synthesis, labeled with an Alexafluor fluorescent dye, and characterized via TEM and fluorescence microscopy. The silica microparticles were functionalized with (3-aminopropyl)trimethoxysilane (APTMS), followed by the use of an established fluorenylmethyloxycarbonyl (Fmoc)-protected PEG-based linker.

High Resolution Structures of the Human ABO(H) Blood Group Enzymes in Complex with Donor Analogs Reveal That the Enzymes Utilize Multiple Donor Conformations to Bind Substrates in a Stepwise Manner.

Homologous glycosyltransferases α-(1→3)-N-acetylgalactosaminyltransferase (GTA) and α-(1→3)-galactosyltransferase (GTB) catalyze the final step in ABO(H) blood group A and B antigen synthesis through sugar transfer from activated donor to the H antigen acceptor. These enzymes have a GT-A fold type with characteristic mobile polypeptide loops that cover the active site upon substrate binding and, despite intense investigation, many aspects of substrate specificity and catalysis remain unclear. The structures of GTA, GTB, and their chimeras have been determined to between 1.

The overall architecture and receptor binding of pneumococcal carbohydrate-antigen-hydrolyzing enzymes.

The TIGR4 and SP3-BS71 strains of Streptococcus pneumoniae each produce family 98 glycoside hydrolases, called Sp4GH98 and Sp3GH98, respectively, which have different modular architectures and substrate specificities. Sp4GH98 degrades the Lewis(Y) antigen and possesses three C-terminal family 47 carbohydrate-binding modules (CBMs) that bind to this substrate. Sp3GH98 degrades the blood group A/B antigens and has two N-terminal family 51 CBMs that are of unknown function.

Synthesis and NMR studies on the ABO histo-blood group antigens: synthesis of type III and IV structures and NMR characterization of type I-VI antigens.

The ABO histo-blood group antigens are best known for their important roles in solid organ and bone marrow transplantation as well as transfusion medicine. Here we report the synthesis of the ABO type III and IV antigens with a 7-octen-1-yl aglycone. Also described is an NMR study of the ABO type I to VI antigens, which were carried out to probe differences in overall conformation of the molecules.

Biocompatible carbohydrate-functionalized stainless steel surfaces: a new method for passivating biomedical implants.

A convenient method for passivating and functionalizing stainless steel is described. Several methods of coating stainless steel (SS) samples with silica were investigated and of these methods, a thin (less than 15 nm thick) layer of silica created by atomic layer deposition (ALD) was found to give superior performance in electrochemical testing. These interfaces were then used as a platform for further functionalization with molecules of biological interest.

Synthesis of ABO histo-blood group type I and II antigens.

The ABO histo-blood group system is one of the most clinically important antigen families. As part of our overall goal to prepare the entire set of the A, B and H type I-VI antigens for a range of biochemical investigations, we report herein the synthesis of the type I and II antigens with a 7-octen-1-yl aglycone. This linker was chosen to facilitate not only the future conjugation of the antigens to a protein or solid support but also the synthesis of the H type I and II octyl glycosides for enzyme kinetic studies.

Glycosyl iodides. History and recent advances.

The use of glycosyl iodides as an effective method for the preparation of glycosides has had a recent resurgence in carbohydrate chemistry, despite its early roots in which these species were believed to be of limited use. Renewed interest in these species as glycosylating agents has been spurred by their demonstrated utility in the stereoselective preparation of O-glycosides, and other glycosylic compounds. This review provides a brief historical account followed by an examination of the use of glycosyl iodides in the synthesis of oligosaccharides and other glycomimetics, including C-glycosylic compounds, glycosyl azides and N-glycosides.

The synthesis of 2-, 3-, 4- and 6-O-alpha-D-glucopyranosyl-D-galactopyranose, and their evaluation as nutritional supplements for pre-term infants.

Four methods have been screened for the synthesis of some alpha-D-glucopyranosides, with the recently reported (Mukaiyama) combination of 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl iodide and triphenylphosphine oxide being the most successful, especially in the diastereoselectivity exhibited. The alpha-D-glucopyranosides so obtained have been deprotected to yield 2-, 3-, 4- and 6-O-alpha-D-glucopyranosyl-D-galactopyranose. Only the last disaccharide showed any hydrolysis by alpha-glycosidases but this success was not emulated by mucosal extracts from the small intestine of the pig.