Synthesis of Bisubstrate Inhibitors of Porphobilinogen Synthase from Pseudomonas aeruginosa

✍ Scribed by Sabine Gacond; Frederic Frère; Merle Nentwich; Jean-Philippe Faurite; Nicole Frankenberg-Dinkel; Reinhard Neier

• Book ID: 101771431
• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 160 KB
• Volume: 4
• Category: Article
• ISSN: 1612-1872
• DOI: 10.1002/cbdv.200790024

✦ Synopsis

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.