title: Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 2: substitution of the glycine part.
abstract: Glutathionylspermidine synthetase (GspS) is an essential enzyme in the biosynthesis of trypanothione and is an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-gamma-Glu-L-Leu-X) where the glycine moiety has been substituted for other amino acids. These peptides were evaluated as substrates and inhibitors of GspS. Compounds with basic side chains such as diaminopropionic acid were found to be good inhibitors (K(i): 7.2 microM). Substitution of the glycine part abolished the GspS substrate properties of the tripeptide.
authors.affiliation: Department of Medicinal Chemistry, University of Antwerp (UIA), Belgium.
authors.forename: Katie
authors.initials: K
authors.lastname: Amssoms
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Oza
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Abdellah
authors.initials: A
authors.lastname: Yamani
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
authors.forename: Gunther
authors.initials: G
authors.lastname: Bal
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Alan H
authors.initials: AH
authors.lastname: Fairlamb
authors.forename: Achiel
authors.initials: A
authors.lastname: Haemers
mesh_terms: D019732:Amide Synthases / Q000037:antagonists & inhibitors*; D019943:Amino Acid Substitution; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D005998:Glycine / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019732:Amide Synthases; C081536:glutathionylspermidine synthetase; D005978:Glutathione; D005998:Glycine