Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 2: substitution of the glycine part.
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.
Amssoms
Katie
K
Department of Medicinal Chemistry, University of Antwerp (UIA), Belgium.
Oza
Sandra L
SL
Augustyns
Koen
K
Yamani
Abdellah
A
Lambeir
Anne-Marie
AM
Bal
Gunther
G
Van der Veken
Pieter
P
Fairlamb
Alan H
AH
Haemers
Achiel
A
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*
D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019732:Amide Synthases; C081536:glutathionylspermidine synthetase; D005978:Glutathione; D005998:Glycine