DEVELOPMENT OF ANTIHEPATITIS B THERAPEUTICS

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. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 54 --PROJECT NUMBER......1 R43 AI40412-01A1 INVESTIGATOR NAME/ADDRESS FY 97 NIEDBALA, R SAMUEL IRG/INTRAMURAL UNIT..ZRG5 STC TECHNOLIES, INC AWARD AMOUNT......... $100,000 1745 EATON AVENUE BETHLEHEM, PA 18018 PERFORMING ORGANIZATION: STC TECHNOLOGIES, INC. TITLE DETECTION OF ORGANISMS USING PHOSPHOR LABELING ABSTRACT: The proposed project will use a new application of phosphorescent materials as the reporter in a capture immunoassay for food-borne pathogens. These inorganic phosphors promise to increase the sensitivity of the assay thus allowing a faster and easier procedure. The phosphors have the unique property of absorbing infrared and emitting visible light (upconversion). Upconversion does not occur in biological molecules, therefore there is no interference with the signal. This, and other features of the phosphors provide a means of developing highly sensitive assays. This increased sensitivity will allow the elimination of the time-consuming culture step required with current methods. We propose to develop a model E-coli 0157:H7 assay, and a breadboard photometer to quantitate the signal. The advantages of this technology will be demonstrated by comparison with commercial, culture-dependent assays. The resulting technological innovation will have significant clinical and commercial potential.