The object of this research is to develop an anti-hepatitis B virus pro-drug which will concentrate in the infected liver tissue by binding the hepatic asialoglycoprotein receptor and releasing the active form of the drug in the hepatocyte. Toward this end, a number of adenosine arabinofuranoside/arabinogalactan conjugates will be synthesized. The conjugates will be evaluated as suitable prodrugs by several critical tests. Interaction with the hepatic asialoglycoprotein receptor in vitro will be determined in a competitive binding assay using isolated rat hepatocytes. The release of adenosine arabinofuranoside, or in some instances, its also active 5 monophosphate derivative, will be measured in vitro also using hepatocyte cell culture A preliminary toxicological examination of the conjugate considered most suitable as a pro-drug will be conducted. The research is expected to lead to an antiviral pro-drug of adenosine arabinofuranoside possessing greater potency and lower toxicity relative to the free drug.Awardee's statement of the potential commercial applications of the research:An effective antiviral agent for hepatitis B viral chronic active hepatitis would fill a medical need for major proportions. About 165 million people world-wide have this disease, for which there is no generally effective therapy, hence a more effective therapeutic would be of great commercial interest.National Institute of Allergy and Infectious Diseases (NIAID)
