Synthesis of bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa
Author(s)
Gacond, Sabine
Frere, Frederic
Nentwich, Merle
Faurite, Jean-Philippe
Frankenberg-Dinkel, Nicole
Date issued
2007
In
Chem. Biodiversity
Vol
2
No
4
From page
189
To page
202
Subjects
Structure-activity relationship (enzyme-inhibiting synthesis of HO2CCH2CH2C(O)CH2XCH2C(O)CH2CH2CO2H (X = O NH S S(O) S(O)2) bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa) porphobilinogen synthase inhibition oxovaleric acid related dicarboxylic acid synthesis
Abstract
Porphobilinogen synthase (PBGS) synthesizes porphobilinogen (PBG), the common precursor of all natural tetrapyrroles, through an asym. condensation of two mols. of 5-aminolevulinic acid (ALA). Sym. linked dimers HO2CCH2CH2C(O)CH2XCH2C(O)CH2CH2CO2H (X = O, NH, S, S(O), S(O)2) derived from ?-oxovaleric acid were synthesized to mimic the assumed bisubstrate bound to the active site of the enzyme. Their inhibition potential was characterized by detn. of the IC50 and Ki values using PBGS from Pseudomonas aeruginosa. The polarity and the size of the functional group X have a strong influence on the inhibition behavior. [on SciFinder(R)]
Publication type
journal article