title: Synthesis and biological activity of new iodoacetamide 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.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, 10125 Torino, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceruti
authors.forename: Gianni
authors.initials: G
authors.lastname: Balliano
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Alexander
authors.initials: A
authors.lastname: Lenhart
authors.forename: Georg E
authors.initials: GE
authors.lastname: Schulz
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
mesh_terms: D001407:Bacillus / Q000201:enzymology; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism*; D007460:Iodoacetamide / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase; D007460:Iodoacetamide