title: Modelling studies of the active site of human sorbitol dehydrogenase: an approach to structure-based inhibitor design of the enzyme.
abstract: The program GRID was used to design novel potential inhibitors of human sorbitol dehydrogenase based on a model of the holoenzyme in complex with the inhibitor WAY135 706. Replacement of the methyl hydroxyl group of the inhibitor with methyl phosphate and methyl carboxylate functional groups increased the net binding energy of the complex by 2.0- and 1.7-fold, respectively. This study may be useful in the development of potent and more specific inhibitors of the enzyme.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, 3052, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Darmanin
authors.forename: O
authors.initials: O
authors.lastname: El-Kabbani
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; C106112:2-hydroxymethyl-4-(4-(N,N-dimethylaminosulfonyl)-1-piperazino)pyrimidine; D007064:L-Iditol 2-Dehydrogenase