Oxford GlycoSystems (OGS) will evaluated two novel types of anti- hepatitis (HB) drugs: Anti-HB drugs conjugates with glycans - Using one-step conjugations adaptable to large-scale manufacturing, OGS is derivitizing anti-retroviral drugs (eg vidarabine, Ara-C, acyclovir, AZT, lamivudine) with glycans recognized by hepatocyte carbohydrate receptors. Similar compounds are targets with high specificity and efficacy into hepatocytes in studies conducted by OGS. For this proposal, OGS will determine if glycan-modification of anti-HB drugs improves how well these agents are internalized by hepatocytes and if their inhibition of HB virus production is increased These studies will lay the foundation for evaluating whether glycan-derivitization of anti-HB drugs overcomes the severe toxicity associated with dosages required to obtain clinical efficacy for unmodified drugs. 2) N-glycan processing inhibitors - The proper processing of N-glycans for HB glycoproteins is required for infectious virus assembly. OGS is developing a wide spectrum of proprietary processing inhibitors to provide a heretofore unprecedented control over the types of N- glycans added to newly synthesized glycoproteins OGS will evaluate how well these processing inhibitors block the production of infectious HB virus I chronically infected hepatocytes.
