Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as s...Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.展开更多
GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an...GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an efficient synthetic route was developed via a [3+2] strategy.The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor,which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone.The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups.Donor bearing the more rigid benzylidene group gave low glycosylation yield.Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide.Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain,which will be a valuable probe for biological studies.展开更多
基金supported by grants and fellowships from the Departamento de Ciência e Tecnologia(DECIT/MS)do Ministério da Saúde,Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa,Fundação de AmparoàPesquisa do Estado do Rio de Janeiro(FAPERJ)(to RMO).
文摘Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.
文摘GM1 is a common ganglioside pentasaccharide present on mammalian cell surface.It has been shown to play important roles in cellular communications and initiation of β-amyloid aggregation.In order to synthesize GM1,an efficient synthetic route was developed via a [3+2] strategy.The GM3 trisaccharide acceptor bearing an azido propyl group at the reducing end was prepared using the traditional acetamide protected sialyl thioglycosyl donor,which gave better stereoselectivity than sialyl donors protected with trichloroacetamide or oxazolidinone.The glycosylation of the axial 4-hydroxyl group of GM3 by the disaccharide donor was found to be highly dependent on donor protective groups.Donor bearing the more rigid benzylidene group gave low glycosylation yield.Replacing the benzylidene with acetates led to productive coupling and formation of the fully protected GM1 pentasaccharide.Deprotection of the pentasaccharide produced GM1 functionalized with the aminopropyl side chain,which will be a valuable probe for biological studies.
