The pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, inhibits glycoprotein processing.

摘要: 2,5-Dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) is a pyrrolidine alkaloid that was isolated from the plant, Lonchocarpus sericeus. In present study, DMDP tested as an inhibitor of glycoprotein processing. MDCK cells were infected with influenza virus and raised in presence various amounts DMDP. The glycoproteins labeled by addition [2-3H]mannose or [1-3H]galactose to medium. differential centrifugation treated Pronase obtain glycopeptides. These glycopeptides chromatography on Bio-Gel P-4, then digested endoglucosaminidase H (Endo H) rechromatographed P-4 column. control virus, more than 70% resistant Endo previously characterized complex types oligosaccharides. remaining 20-25% are sensitive high-mannose type. However, (250 micrograms/ml), 80% susceptible digestion H. oligosaccharide released this treatment sized like hexose11-12GlcNAc calibrated column only slightly alpha-mannosidase treatment. This also glucose moieties growing Following isolation, subjected complete methylation. Acid hydrolysis methylated gave three derivatives, corresponding 2,3,4,6-tetramethylglucose, 3,4,6-trimethylglucose, 2,4,6-trimethylglucose almost equal amounts. data indicate Glc3Man8-9-GlcNAc inhibits glucosidase I. Similar results obtained cellular glycoproteins. did not inhibit incorporation [3H]leucine into protein cells, nor it production measured plaque counts hemagglutination assays. cause some inhibition mannose lipid-linked monosaccharides, but oligosaccharides greatly affected, stimulated. suggest alkaloids new class processing inhibitors.