title: Phosphonate inhibitors of antigen 85C, a crucial enzyme involved in the biosynthesis of the Mycobacterium tuberculosis cell wall.
abstract: The first phosphonate inhibitors of antigen 85C--a major protein component of the Mycobacterium tuberculosis cell wall possessing mycolyltransferase activity were prepared using structure-based design. These potential novel antituberculosis agents, consisting of a phosphonate moiety, hydrophobic alkyl chain and a simple trehalose-mimicking aromatic structure, were designed as tetrahedral transition-state analogue inhibitors of antigen 85C, which catalyzes the key mycolyltransferase reaction involved in cell wall biosynthesis.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. gobecs@ffa.uni-lj.si
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Ivan
authors.initials: I
authors.lastname: Plantan
authors.forename: Janez
authors.initials: J
authors.lastname: Mravljak
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Wilson
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002384:Catalysis; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D018716:Molecular Mimicry; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000378:metabolism*; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D006841:Hydrocarbons, Aromatic; D063065:Organophosphonates; D000217:Acyltransferases; C119774:antigen 85C, Mycobacterium tuberculosis; C053820:trehalose mycolyltransferase