Phosphonate inhibitors of antigen 85C, a crucial enzyme involved in the biosynthesis of the Mycobacterium tuberculosis cell wall.
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.
Gobec
Stanislav
S
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. gobecs@ffa.uni-lj.si
Plantan
Ivan
I
Mravljak
Janez
J
Wilson
Rosalind A
RA
Besra
Gurdyal S
GS
Kikelj
Danijel
D
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*
D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D006841:Hydrocarbons, Aromatic; D063065:Organophosphonates; D000217:Acyltransferases; C119774:antigen 85C, Mycobacterium tuberculosis; C053820:trehalose mycolyltransferase