title: eta(1)-N-succinimidato complexes of iron, molybdenum and tungsten as reversible inhibitors of papain.
abstract: Recently we have found that the metallocarbonyl complexes (eta(5)-C(5)H(5))M(CO)(x)(eta(1)-N-maleimidato) (M=Fe, Mo, W; x=2 or 3) bearing a maleimide function were irreversible inhibitors of the enzyme papain. To get further insight into the binding mechanism of these compounds we synthesized the related complexes (eta(5)-C(5)H(5))M(CO)(x)(eta(1)-N-succinimidato) (M=Fe, Mo, W; x=2 or 3) that lacked the ethylenic bond responsible for alkylation of the cysteine 25 thiol group in the papain's catalytic pocket. We performed kinetic studies of the interaction of the synthesized complexes towards papain. We found that they act as reversible inhibitors of the enzyme with IC(50) values in the range 480-1700microM. Docking experiments confirmed binding of these complexes to the enzyme's catalytic pocket.
authors.affiliation: Department of Organic Chemistry, University of Łódź, Poland. brudolf@chemul.uni.lodz.pl
authors.forename: Bogna
authors.initials: B
authors.lastname: Rudolf
authors.forename: Michèle
authors.initials: M
authors.lastname: Salmain
authors.forename: Annie
authors.initials: A
authors.lastname: Martel
authors.forename: Marcin
authors.initials: M
authors.lastname: Palusiak
authors.forename: Janusz
authors.initials: J
authors.lastname: Zakrzewski
mesh_terms: D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007501:Iron / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008982:Molybdenum / Q000737:chemistry*; D010206:Papain / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014414:Tungsten / Q000737:chemistry*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D013388:Succinimides; D008982:Molybdenum; D007501:Iron; D010206:Papain; D014414:Tungsten