title: Synthesis of bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa.
abstract: Porphobilinogen synthase (PBGS) synthesizes porphobilinogen 2 (PBG), the common precursor of all natural tetrapyrroles, through an asymmetric condensation of two molecules of 5-aminolevulinic acid 1 (ALA). Symmetrically linked dimers 7-11 derived from levulinic acid 3 (gamma-oxovaleric acid) have been synthesized to mimic the assumed bisubstrate bound to the active site of the enzyme. Their inhibition potential was characterized by determination of the IC(50) and K(i) values using PBGS from Pseudomonas aeruginosa. The polarity and the size of the functional group linking the two levulinic acid 3 units have a strong influence on the inhibition behavior.
authors.affiliation: Institute of Chemistry, University of Neuchâtel, Neuchâtel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Gacond
authors.forename: Frederic
authors.initials: F
authors.lastname: Frère
authors.forename: Merle
authors.initials: M
authors.lastname: Nentwich
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Faurite
authors.forename: Nicole
authors.initials: N
authors.lastname: Frankenberg-Dinkel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Neier
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000623:Porphobilinogen Synthase