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ID: ALA1155510

Journal: Bioorg Med Chem Lett

Title: Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited.

Authors: Tang J, Maddali K, Pommier Y, Sham YY, Wang Z.

Abstract: A series of dihydroxypyrimidine (DHP) derivatives were designed as inhibitors of HIV integrase (IN) based on known homology models. Through chemical synthesis and biochemical assays it was found that the activity profile of these compounds largely deviates from predictions with existing models. With the recently disclosed IN crystal structure of prototype foamy virus (PFV), a new HIV IN homology model was constructed featuring a critical IN/DNA interface previously lacking. With this new model, docking results completely corroborated observed biological activities. This new model should provide a more accurate and improved platform for the design of new inhibitors of HIV IN.

CiteXplore: 20457521

DOI: 10.1016/j.bmcl.2010.04.048