mannosylretinylphosphate and Cell-Transformation--Viral

The guanosine diphosphate 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-acetyl-chitobiose 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 dolichol-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 FGlc from GDP-FGlc incorporated into retinol-phosphate-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.

Topics: Animals; Carbon Radioisotopes; Cell Transformation, Viral; Cells, Cultured; Chick Embryo; Deoxy Sugars; Deoxyglucose; Diterpenes; Guanosine Diphosphate Mannose; Kinetics; Microsomes, Liver; Orthomyxoviridae; Polyisoprenyl Phosphate Monosaccharides; Polyisoprenyl Phosphate Sugars; Rats; Vitamin A