Chemical or chemoenzymatic synthesis is an emerging approach to produce homogeneous glycoproteins with structurally defined forms. Modern synthetic techniques are capable of the preparation of complex glycoproteins. This minireview especially focuses on the several latest syntheses of N-glycoproteins that generally have relatively large glycan moieties. The structurally defined glycoproteins can be a novel material for understanding molecular basis of glycoprotein functions or the next generation of biopharmaceuticals.
Glycans are essential components of higher organisms, exhibiting highly sophisticated expression and complex functions. In particular, unique glycan structures are highly expressed in the nervous system, and play essential roles in higher order brain functions such as learning and memory. In this review, I focus on three unique neural glycans, namely, human natural killer-1 (HNK-1) epitope, branched O-mannose glycans, and bisecting GlcNAc, and describe regulation of their expression, what functions they exhibit, and how they are involved in various neural diseases including demyelination and dementia. Various mechanisms are involved in regulation of their expression, including enzyme complex formation, enzyme localization, alternative splicing, and (epi)genetics. Furthermore, mutant mice deficient for these glycans display improved pathology in demyelination and dementia, suggesting that biosynthetic pathways for these glycans could be novel targets for disease therapy. Further understanding of their function and development of new probes and inhibitors for these glycans may lead to future novel strategies for basic and clinical glycosciences.
In the nervous system, there are a number of oligosaccharides associated with neural-cell differentiation and higher-order brain functions. To examine these functions, it has been developed useful glycomics tools, including a sugar library and a novel sequencing method, for functional glycomics in the nervous system. These glycemic tools have enable us to find neural-specific glycan in the model organism Ciona intestinalis and demonstrat the function of specific glycans related to neural stem-cell differentiation and a laminin binding glycans that cause congenital muscular dystrophies.
Chemical or chemoenzymatic synthesis is an emerging approach to produce homogeneous glycoproteins with structurally defined forms. Modern synthetic techniques are capable of the preparation of complex glycoproteins. This minireview especially focuses on the several latest syntheses of N-glycoproteins that generally have relatively large glycan moieties. The structurally defined glycoproteins can be a novel material for understanding molecular basis of glycoprotein functions or the next generation of biopharmaceuticals.
Glycans are essential components of higher organisms, exhibiting highly sophisticated expression and complex functions. In particular, unique glycan structures are highly expressed in the nervous system, and play essential roles in higher order brain functions such as learning and memory. In this review, I focus on three unique neural glycans, namely, human natural killer-1 (HNK-1) epitope, branched O-mannose glycans, and bisecting GlcNAc, and describe regulation of their expression, what functions they exhibit, and how they are involved in various neural diseases including demyelination and dementia. Various mechanisms are involved in regulation of their expression, including enzyme complex formation, enzyme localization, alternative splicing, and (epi)genetics. Furthermore, mutant mice deficient for these glycans display improved pathology in demyelination and dementia, suggesting that biosynthetic pathways for these glycans could be novel targets for disease therapy. Further understanding of their function and development of new probes and inhibitors for these glycans may lead to future novel strategies for basic and clinical glycosciences.
In the nervous system, there are a number of oligosaccharides associated with neural-cell differentiation and higher-order brain functions. To examine these functions, it has been developed useful glycomics tools, including a sugar library and a novel sequencing method, for functional glycomics in the nervous system. These glycemic tools have enable us to find neural-specific glycan in the model organism Ciona intestinalis and demonstrat the function of specific glycans related to neural stem-cell differentiation and a laminin binding glycans that cause congenital muscular dystrophies.