Protein C-Mannosylation is unique in that an α-mannose attaches directly to the indole C2 carbon atom of a Trp residue through a C-C bond. C-Mannosylation usually occurs at the first tryptophan in the consensus amino acid sequence Trp-x-x-Trp (W-x-x-W) through an enzymatic reaction with a specific mannosyltransferase, which has yet to be identified. Most substrates for C-mannosylation are part of either the thrombospondin type-1 repeat (TSR) superfamily or cytokine receptor family, suggesting a functional role for C-mannosylation in specific substrates. Site-directed mutagenesis in the W-x-x-W motif has revealed C-mannosylation to be important in the folding or targeting of substrate proteins, such as mucins and ADAMTS-like 1, in the cell. Furthermore, using chemically synthesized C-mannosylated TSR-derived peptides, Hsc70 was identified as a protein bound to C-mannosylated peptides, and the interaction enhanced the TNF-α-producing signaling by Hsc70 in macrophage-like cells. These recent findings suggest that the C-mannosylation of specific target proteins plays pivotal functional roles in the cell.

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Sialic acids (Neu5Ac, 1) are involved in many biological functions of glycoproteins, glycolipids, and cells. Sialidases are a family of glycosidases that catalyze the removal of α-glycosidically linked sialic acid residues from carbohydrate groups of glycoconjugates. Among the compounds related to the sialic acid family, 2-deoxy-2,3-dehydro-N-acetylneuraminic acids (Neu5Ac2en, 2) are known to inhibit sialidases. Human parainfluenza viruses are important respiratory tract pathogens, particularly in children. However, no vaccines or specific therapies for infections caused by these viruses are currently available. This article reviews our progress and current trends of the modification of 2-deoxy-2,3-didehydro sialic acid analogs and biological evaluations of their inhibitory activities against human parainfluenza virus type 1 (hPIV-1) sialidases.

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Major advances have been made in exploring the trans-glycosylation activity of endo-β-N--acetylglucosaminidases (ENGases) for synthetic purpose. The exploration of synthetic sugar oxazolines as donor substrates for the ENGase-catalyzed transglycosylation has expanded the substrate availability and significantly enhanced the overall transglycosylation efficiency. On the other hand, site-directed mutagenesis in combination with activity screening has led to the discovery of the first generation ENGase-based glycosynthases that can use highly active sugar oxazolines as substrates for transglycosylation but lack hydrolytic activity on the ground-state products. ENGases have shown amazing flexibility in transglycosylation and possess much broader substrate specificity than previously thought. Now the ENGase-based chemoenzymatic method has been extended to the synthesis of a range of complex carbohydrates, including homogeneous glycopeptides, glycoproteins carrying well-defined glycans, novel oligosaccharide clusters, unusually glycosylated natural products, and even polysaccharides. This article highlights recent advances related to ENGase-catalyzed transglycosylation with a focus on their synthetic potential.

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Effects of potentially participating groups at remote positions of glycopyranosyl and glycofuranosyl donors on the glycosylation stereochemistry are reviewed. Substantial evidences in favor of the remote participation by protecting groups are presented and also included are a few reports opposed to the remote participation.

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