title: Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited.
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.
authors.affiliation: Center for Drug Design, Academic Health Center, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Kasthuraiah
authors.initials: K
authors.lastname: Maddali
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Yuk Y
authors.initials: YY
authors.lastname: Sham
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D011743:Pyrimidines
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