Abstract
The guanosine disphospate and uridine diphosphate esters of the antiviral sugar analog 2-deoxy-2-fluoro-D-glucose (GDP-FGlc and UDP-FGlc) were synthesized and tested as inhibitors of formation of lipid-linked sugars in cell-free extracts . Formation of dolichol-phosphate mannose and of dolichol-diphosphate di-N-acetylchitobiose were not inhibited by either sugar nucleotide. Formation of dolichol-phosphate glucose was inhibited by UDP-FGlc, not by GDP-FGlc. Although GDP-FGlc did not inhibit formation of dollchol-phosphate mannose, it did inhibit formation of retinol-phosphate mannose from retinol-phosphate and GDP-Man. This inhibition was not reversed by exogenous retinol-phosphate, nor was FGIc from GDP-FGlc incorporated into retinolphosphate-linked derivatives. As FGLc inhibits formation of dolichol-phosphate mannose in intact cells, but does not decrease pool sizes of GDP-Man and dolichol-phosphate (Datema et al., 1980, Eur. J. Biochem.109, 331–341), we discuss that inhibition of formation of retinol-phosphate mannose by one of the metabolites of FGlc, namely GDP-FGlc, may lead to decreased synthesis of dolichol-phosphate mannose in FGlc-treated cells. This implies a role for vitamin A in the dolichol cycle of protein glycosylation.
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Datema, R., Schwarz, R.T. An inhibitor of mannosylation of retinyl-phosphate. Biosci Rep 4, 213–221 (1984). https://doi.org/10.1007/BF01119656
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DOI: https://doi.org/10.1007/BF01119656