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-γ-Glu-L-Leu-Gly-X) where the glycine...

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Detalles Bibliográficos
Autores principales: Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.-M., Rajan, P., Bal, G., Rodriguez, J.B., Fairlamb, A.H., Augustyns, K., Haemers, A.
Formato: JOUR
Materias:
acylsulfonamide
amide
boronic acid derivative
carboxylic acid
enzyme inhibitor
glutathione
glutathione derivative
glutathionylspermidine synthethase
glycine
hydroxamic acid
synthetase
tetrazole derivative
tripeptide
unclassified drug
acidity
amino acid substitution
amino acid synthesis
article
IC 50
protein analysis
Amide Synthases
Carboxylic Acids
Enzyme Inhibitors
Glutathione
Glycine
Oligopeptides
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0960894X_v12_n18_p2553_Amssoms
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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-γ-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 (IC50 of 17.2 μM). © 2002 Elsevier Science Ltd. All rights reserved.

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