Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group.
Glutathionylspermidine synthetase/amidase (GspS) is an essential enzyme in the biosynthesis and turnover of trypanothione and represents an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-gamma-Glu-L-Leu-Gly-X) where the glycine carboxylic acid group (X) has been substituted for other acidic groups such as tetrazole, hydroxamic acid, acylsulphonamide and boronic acid. The boronic acid appears the most promising lead compound (IC(50) of 17.2 microM).
Amssoms
Katie
K
Department of Medicinal Chemistry, University of Antwerp (UIA), Belgium.
Oza
Sandra L
SL
Ravaschino
Esteban
E
Yamani
Abdellah
A
Lambeir
Anne
A
Rajan
Padinchare
P
Bal
Gunther
G
Rodriguez
Juan
J
Fairlamb
Alan H
AH
Augustyns
Koen
K
Haemers
Achiel
A
D019732:Amide Synthases / Q000037:antagonists & inhibitors*; D002264:Carboxylic Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology*; D005998:Glycine / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019732:Amide Synthases; C081536:glutathionylspermidine synthetase; D005978:Glutathione; D005998:Glycine