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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Modular Synthesis of Nucleoside Diphosphate Sugar Analogues Using Chlorosulfonyl Isocyanate and Dichlorophosphoryl
Roy Steneker1, Koen J Rijpkema1, Tim P Ofman1
1Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
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Pyrophosphates are central to biology, and synthetic pyrophosphate isosteres are widely sought to create biomimetic molecules to study diverse biochemical processes. We describe a flexible, modular synthesis of nucleoside diphosphate sugar analogues by linking carbasugars and nucleosides with the dual electrophilic reagents chlorosulfonyl isocyanate and dichlorophosphoryl isocyanate, introducing sulfonyl- and phosphoryl-carbamate linkages as pyrophosphate isosteres, respectively. The resulting GDP-fucose and UDP-GlcNAc analogues may inhibit glycosyltransferases and serve as tools for studying pyrophosphate-processing enzymes.
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