Synthesis and biological activity of new lodoacetamide derivatives on mutants of squalene‐hopene cyclase

Abstract New iodoacetamide derivatives, containing a dodecyl or a squalenyl moiety, were synthesized. The effect of these new thiol‐reacting molecules was studied on two mutants of Alicyclobacillus acidocaldarius squalene‐hopene cyclase constructed especially for this purpose. In the quintuple mutant, all five cysteine residues of the enzyme are substituted with serine; in the sextuple mutant, this quintuple substitution is accompanied by the substitution of aspartate D376, located at the enzyme's active site, with a cysteine. N ‐Dodecyliodoacetamide had little activity toward either mutant, whereas N ‐squalenyliodoacetamide showed a stronger effect on the sextuple than on the quintuple mutant, as expected.