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• W2078754833 startingPage "17394" @default.
• W2078754833 abstract "Although hundreds of heparan sulfate binding proteins have been identified and implicated in a myriad of physiological and pathological processes, very little information is known about the ligand requirements for binding and mediating biological activities by these proteins. This difficulty results from a lack of technology for establishing structure−activity relationships, which in turn is due to the structural complexity of natural heparan sulfate (HS) and difficulties of preparing well-defined HS oligosaccharides. To address this deficiency, we developed a modular approach for the parallel combinatorial synthesis of HS oligosaccharides that utilizes a relatively small number of selectively protected disaccharide building blocks, which can easily be converted into glycosyl donors and acceptors. The utility of the modular building blocks has been demonstrated by the preparation of a library of 12 oligosaccharides, which has been employed to probe the structural features of HS for inhibiting the protease, BACE-1. The complex variations in activity with structural changes support the view that important functional information is embedded in HS sequences. Furthermore, the most active derivative provides an attractive lead compound for the preparation of more potent compounds, which may find use as a therapeutic agent for Alzheimer’s disease." @default.
• W2078754833 created "2016-06-24" @default.
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• W2078754833 creator A5076407370 @default.
• W2078754833 creator A5087509293 @default.
• W2078754833 date "2009-11-11" @default.
• W2078754833 modified "2023-10-17" @default.
• W2078754833 title "Modular Synthesis of Heparan Sulfate Oligosaccharides for Structure−Activity Relationship Studies" @default.
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• W2078754833 doi "https://doi.org/10.1021/ja907358k" @default.
• W2078754833 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2820250" @default.
• W2078754833 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19904943" @default.
• W2078754833 hasPublicationYear "2009" @default.
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