Development of Aminoglycoside Based HIV Therapeutics

The goal of this research is to synthesize orally active derivatives of a lead compound, neomycin Breplication of the AIDS virus at the level of transcription by inhibiting the Rev protein/RRE interabetween this protein and sequence of nucleic acid is crucial to the virus life cycle. Recent work hasmall molecule antibiotic neomycin B is capable of disrupting the binding of Rev to the RRE. Such aneffective therapeutic for HIV. However, neomycin B needs improvement in such areas as its cytotoxicispecificity for the Rev/RRE interaction. Also, syntheses of the large number of compounds necessarywould be time consuming and difficult using existing literature methods due to the highly functionalof the lead compound. We will approach this problem by the production of appropriately protected syncommercially available ribostamycin as a starting material. This approach will allow one to produceneomycin analogs expediently by appending D-ring analogs of wide functional and structural diversitymultiple assays exist in house to provide activity data on all analogs.