| 摘要 |
Selecting (M1) compounds (I) that bind to the mycobacterial repressor EthR, preventing it from repressing expression of the ethA gene, which encodes the EthA protein that activates ethionamide (II; 2-ethylthioisonicotinamide), comprising cloning the repressor gene in a plasmid, growing transformants in presence of test compound, and selecting compound based on level of reporter gene detected, is new.. Selecting compounds (I) that bind to the mycobacterial repressor EthA, preventing it from repressing expression of the ethA gene, encoding the EthA protein that activates ethionamide (II; 2-ethylthioisonicotinamide) comprises: (a) cloning the repressor gene in a first recombinant plasmid (P1) and cloning at least one promoter/operator region of the same gene upstream of a reporter gene in a second plasmid (P2), or cloning both the repressor gene and the promoter/operator gene into a single plasmid; (b) transforming a host cell with both plasmids; (c) growing transformants in presence of a test compound (III); (d) measuring the level of reporter gene in presence of (III) and comparing it with the level in absence of test compound; and (e) selecting (III) if the level of reporter gene in presence of (II) is significantly greater than the level in the absence of (II). Independent claims are also included for: (1) selecting (M2) (I) comprising determining the level (L1) of binding of the EthR repressor to at least one promoter/operator gene in presence of (III), comparing this with the level (L0) in absence of test compound and selecting (II) if L1 is significantly lower than L0. ACTIVITY : Antitubercular; Tuberculostatic; Antileprotic. No biological data given. MECHANISM OF ACTION : Inactivation of the EthR repressor. |
