Glutathione-like Tripeptides as Inhibitors of Glutathionylspermidine Synthetase: 1. Substitution of the Glycine Carboxylic Acid Group.

AMSSOMS, KATIE; OZA, SANDRA L.; RAVASCHINO, ESTEBAN LUIS; YAMANI, ABDELLAH; LAMBEIR, ANNE-MARIE; RAJAN, PADINCHARE; BAL, GUNTHER; RODRIGUEZ, JUAN BAUTISTA; FAIRLAMB, ALAN H.; AUGUSTYNS, KOEN; HAEMERS, ACHIEL

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2002 vol. 12 p. 2553 - 2556

0960-894X

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-g-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 mM).