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Synthesis of Bisubstrate Inhibitors of Porphobilinogen Synthase from Pseudomonas aeruginosa
Author(s) -
Gacond Sabine,
Frère Frederic,
Nentwich Merle,
Faurite JeanPhilippe,
FrankenbergDinkel Nicole,
Neier Reinhard
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790024
Subject(s) - porphobilinogen , levulinic acid , porphobilinogen synthase , chemistry , dehydratase , enzyme , atp synthase , stereochemistry , biochemistry , molecule , active site , organic chemistry , catalysis
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 ( γ ‐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.