Glutathionylspermidine Synthetase/Amidase

Goal: To aid in the development of new potent anti-parasitic drugs.

Trypanothione (TSH), found exclusively in trypanosomatid parasites, is a derivative of the ubiquitous antioxidant, glutathione (GSH). The biosynthesis of TSH involves bis-acylation of the polyamine, spermidine, by GSH. The intermediate monoacylated GSH, glutathionylspermidine (Gsp), but not TSH, is found in E. coli and both its synthesis and hyrdrolysis are effected by a unique bifunctional enzyme, Gsp synthetase/amidase. We have extended our phosphapeptide research mentioned above to the development of new inhibitors of TSH biosynthesis as possible anti-trypanosomal drugs. Based on an understanding of the mechanism of Gsp synthetase/amidase, we have designed and synthesized specific phosphapeptide inhibitors of the synthetase domain and, in collaborative research, have used these compounds to study the regulation of catalysis by this bifunctional enzyme.

Researchers interested in Trypanothione

Alan Fairlamb at the University of Dundee.

If you are a researcher interested in trypanathione or related topics please drop us a note and we will add you to our list!

 
Last updated: March 2003
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S. Anspaugh, anspaugh@umich.edu