Tuesday, 27 June 2006
Ponderosa (poster/exhibit) (John Ascuaga’s Nugget Casino Resort)
202

Synthesis of potential nucleoside inhibitors of HIV/HTLV integrase

Pucheng Ke and Matt A. Peterson. Brigham Young University, Provo, UT

Viral integrase (IN) enzymes such as HIV-IN and HTLV-IN (human T-cell leukemia virus integrase) are key enzymes involved in viral replication and are therefore attractive targets for development of antiviral chemotherapeutic agents.  The active site of HIV-IN is well characterized and X-ray crystal structures of the catalytic domain allow structure-based drug design via virtual library screening (ligand docking) and traditional medicinal chemistry approaches.  Here, we describe the synthesis of a small library of adenosine derivatives whose structures were indicated by docking an approximately 50,000-member virtual library (FLEXX, Sybyl 6.9, Tripos, Inc.) against the active site of HIV-IN (crystal structure 1BIU, Protein Databank).  The synthetic library consisted of adenosine analogues 2 readily prepared from 3'-C functionalized adenosine derivative 1.  Synthetic details and preliminary biological data will be presented.

 

 

 


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