Trypanothione disulfide

During the past decade the development of novel protection groups for the directed protection of primary and secondary amines led to a large improvement of the linkers and resins to serve the different needs. The first solid phase syntheses of polyamines were reported by Sergheraert and coworkers [156]. The synthesis of reduced trypanothione disulfide (45) and its oxidized form (46) involved the selective protection of the primary amines of spermidine with a ferf-butyldiphenylsilyl (TBDPS)... 

Figure 3-7. Sequence alignment of various enzymes in the flavopro-tein disulfide oxidoreductase family. The sequences of the NADP4-dependent enzymes are the glutathione reductase from E. coli (E-GR), human (H-GR), Pseudomonas aeruginosa (P-GR), mercuric reductase from Staphylococcus aureus (S-MR), P. aeruginosa Tn 501 (P-GR), and trypanothione reductase from Trypanosoma congolense (T-TR). The NAD+-dependent enzymes are dihydrolipoamide dehydrogenase from E. coli (E-DD), B. stearothermophilus (B-DD), yeast (Y-DD), and human (H-DD). Residue positions marked with an asterisk correspond to those that were targets of site-directed mutagenesis in the text.

C. fasciculata (52-54) and T. cruzi (55-57). The enzyme, which has been found located only in the cytosol of T. brucei (58), catalyzes the NADPH-dependent reduction of trypanothione, but not glutathione. Ultimately, dihydrotrypanothione is capable of undergoing a rapid non-enzymatic disulfide exchange reaction with intracellular disulfides (RSSR), among them oxidized glutathione and cysteine (59). This reaction is summarized as ... 

Shames, S. L., Fairlamb, A. H., Cerami, A. and Walsh, C. T. (1986) Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry 25 3519-3526. 

---