title: Synthesis and enzymology of modified N-benzyloxycarbonyl-L-cysteinylglycyl-3,3-dimethylaminopropylamide++ + disulphides as alternative substrates for trypanothione reductase from Trypanosoma cruzi: Part 3.
abstract: Kinetic data for alternative substrates of recombinant trypanothione reductase from Trypanosoma cruzi were measured for a series of N-substituted-L-cysteinylglycyl-3-dimethylaminopropylamides, in which the cysteine N-substituent was either a variant of the benzyloxycarbonyl group or was L-phenylalanine or L-tryptophan. Replacing the benzylic ether oxygen atom by CH2 or NH had relatively minor effects on kcat, but raised the value of K(m) 4.5- and 10-fold, respectively. Similarly, relative to the carbobenzoxy group, an N-L-phenylalanyl or N-L-tryptophanyl replacement on the cysteine hardly altered kcat, but increased K(m) values by 16.6 and 7.4 fold, respectively. These observations were consistent with the K(m) values referring primarily to binding for this series of nonspecific substrates.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Manchester, United Kingdom.
authors.forename: C T
authors.initials: CT
authors.lastname: Yuen
authors.forename: J
authors.initials: J
authors.lastname: Garforth
authors.forename: T
authors.initials: T
authors.lastname: Besheya
authors.forename: R
authors.initials: R
authors.lastname: Jaouhari
authors.forename: J H
authors.initials: JH
authors.lastname: McKie
authors.forename: A H
authors.initials: AH
authors.lastname: Fairlamb
authors.forename: K T
authors.initials: KT
authors.lastname: Douglas
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D004220:Disulfides / Q000138:chemical synthesis* / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D004220:Disulfides; C028505:cysteinylglycine; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005978:Glutathione; D010100:Oxygen