Comparison of the Inhibition of Yeast, Rat, and Human Squalene Synthetase

✍ Scribed by P.V. Lograsso; S. Cornellkennon; B.R. Boettcher

• Book ID: 102563811
• Publisher: Elsevier Science
• Year: 1994
• Tongue: English
• Weight: 278 KB
• Volume: 22
• Category: Article
• ISSN: 0045-2068
• DOI: 10.1006/bioo.1994.1023

✦ Synopsis

A comparison of the inhibition of yeast, rat, and human squalene synthetase (SQS) by zaragozic acid (\mathrm{C}) and two farnesyl pyrophosphate (FPP) analogs was made. (\mathrm{IC}{50}) values measured at steady state revealed that zaragozic acid (\mathrm{C}) was a nanomolar inhibitor of all three isozymes. The isoprenoid (phosphinylmethyl) phosphonate (266056), an FPP analog which has the allylic and anhydride oxygen atoms replaced with (\mathbf{C H}{2}), was a micromolar inhibitor of all three isozymes. An exception to the above trends was seen with an etherlinked (phosphinylmethyl) phosphonate (267338). This compound was between 15- and 42fold more potent an inhibitor of the mammalian forms of SQS than it was for yeast squalene synthetase, suggesting potential differences in active-site binding residues. O 1994 Academic Press, Inc.