Mammalian cells express a variety of glycans on their cell surface. The pattern of the expressed glycans is closely regulated by glycosyltransferases, their doners and acceptors, glycosidases and related systems. In pre-disease and disease conditions, it is well known that the pattern of the expression of glycans is altered and unusual glycans are frequently generated, which leads to the disruption in glycan homeostasis. In cancer, the ectopic expression of those unusual glycans has been identified and they are considered to be cancer biomarkers and therapeutic targets. Here, I review the molecular functions of ganglioside GD3 and the heparan sulfate glycosaminoglycan for enhancing the malignant phenotypes of glioma. The expression of these glycans on the cell surface strengthens cell signaling that is transduced through receptor type of tyrosine kinases (RTKs), especially the platelet-derived growth factor receptor α (PDGFRα). A concise discussion regarding the possibility of the development of GD3- or heparan sulfate glycosaminoglycan-targeting therapies for patients suffering from glioma is also included.

Gangliosides are the components of lipid rafts involved in several biological events such as signal transduction. The synthesis of structurally well-defined gangliosides is necessary in order to elucidate the formation mechanisms and functions of lipid rafts at the molecular level. However, previous methods to achieve stereocontrol in glycosidic bond formation of sialic acid have shown that it is substrate-dependent. Therefore, the chemical synthesis of gangliosides and their glycans remains a challenging task in carbohydrate chemistry. This review presents the development of a 1,5-lactam synthetic strategy for gangliosides.

Polysialic acid is a linear homopolymer of sialic acid that is widely expressed in the fetal brain but is expressed only in some limited regions of the adult brain where somehow remain a high degree of neuroplasticity. Conventionally, it is considered to be an anti-adhesion molecule owing to its physicochemical properties. However, it has recently been shown that it directly binds bioactive molecules involved in brain development and higher brain functions and comprehensively regulates their actions near the cell surface. Recently, postmortem brain and large-scale comparative genomic analyses have revealed an association between polysialic acid and its biosynthetic enzyme, ST8SIA2, and psychiatric disorders. In this review, I discuss polysialic acid and the effects of various single nucleotide polymorphisms (SNPs) on ST8SIA2, focusing on the results of biochemical analyses.

Lysosomes are cellular organelles that decompose biomacromolecules, such as nucleic acids, proteins, lipids, and sugars, generated inside and outside of cells. The inside of lysosomes is maintained acidic and lysosomes contain approximately 60 types of acid hydrolases. When a defect in the genes encoding lysosomal enzymes, or in the genes encoding proteins involved in the intracellular transport of these enzymes, occurs, substrates accumulate in the cells, resulting in lysosomal storage diseases. Currently, enzyme replacement therapy is the most common treatment for lysosomal storage diseases. Enzyme replacement therapy is performed by intravenous administration of recombinant lysosomal enzymes produced in vitro. Mannose-6-phosphate receptors and mannose receptors are involved in the intracellular uptake of these recombinant lysosomal enzymes, and N-linked glycan structures on the recombinant lysosomal enzymes contribute to the uptake efficiency. This review outlines enzyme replacement therapies and discusses the current state of the glycan engineering of recombinant lysosomal enzymes.

Mammalian cells express a variety of glycans on their cell surface. The pattern of the expressed glycans is closely regulated by glycosyltransferases, their doners and acceptors, glycosidases and related systems. In pre-disease and disease conditions, it is well known that the pattern of the expression of glycans is altered and unusual glycans are frequently generated, which leads to the disruption in glycan homeostasis. In cancer, the ectopic expression of those unusual glycans has been identified and they are considered to be cancer biomarkers and therapeutic targets. Here, I review the molecular functions of ganglioside GD3 and the heparan sulfate glycosaminoglycan for enhancing the malignant phenotypes of glioma. The expression of these glycans on the cell surface strengthens cell signaling that is transduced through receptor type of tyrosine kinases (RTKs), especially the platelet-derived growth factor receptor α (PDGFRα). A concise discussion regarding the possibility of the development of GD3- or heparan sulfate glycosaminoglycan-targeting therapies for patients suffering from glioma is also included.

Gangliosides are the components of lipid rafts involved in several biological events such as signal transduction. The synthesis of structurally well-defined gangliosides is necessary in order to elucidate the formation mechanisms and functions of lipid rafts at the molecular level. However, previous methods to achieve stereocontrol in glycosidic bond formation of sialic acid have shown that it is substrate-dependent. Therefore, the chemical synthesis of gangliosides and their glycans remains a challenging task in carbohydrate chemistry. This review presents the development of a 1,5-lactam synthetic strategy for gangliosides.

Polysialic acid is a linear homopolymer of sialic acid that is widely expressed in the fetal brain but is expressed only in some limited regions of the adult brain where somehow remain a high degree of neuroplasticity. Conventionally, it is considered to be an anti-adhesion molecule owing to its physicochemical properties. However, it has recently been shown that it directly binds bioactive molecules involved in brain development and higher brain functions and comprehensively regulates their actions near the cell surface. Recently, postmortem brain and large-scale comparative genomic analyses have revealed an association between polysialic acid and its biosynthetic enzyme, ST8SIA2, and psychiatric disorders. In this review, I discuss polysialic acid and the effects of various single nucleotide polymorphisms (SNPs) on ST8SIA2, focusing on the results of biochemical analyses.

Lysosomes are cellular organelles that decompose biomacromolecules, such as nucleic acids, proteins, lipids, and sugars, generated inside and outside of cells. The inside of lysosomes is maintained acidic and lysosomes contain approximately 60 types of acid hydrolases. When a defect in the genes encoding lysosomal enzymes, or in the genes encoding proteins involved in the intracellular transport of these enzymes, occurs, substrates accumulate in the cells, resulting in lysosomal storage diseases. Currently, enzyme replacement therapy is the most common treatment for lysosomal storage diseases. Enzyme replacement therapy is performed by intravenous administration of recombinant lysosomal enzymes produced in vitro. Mannose-6-phosphate receptors and mannose receptors are involved in the intracellular uptake of these recombinant lysosomal enzymes, and N-linked glycan structures on the recombinant lysosomal enzymes contribute to the uptake efficiency. This review outlines enzyme replacement therapies and discusses the current state of the glycan engineering of recombinant lysosomal enzymes.