Development of an efficient enzymatic production of gamma-D-glutamyl-L-tryptophan (SCV-07), a prospective medicine for tuberculosis, with bacterial gamma-glutamyltranspeptidase.

Abstract

Gamma-D-Glutamyl-L-tryptophan (SCV-07) is a prospective medicine for the treatment of tuberculosis, according to the phase two clinical trial. Because gamma-D-glutamyl-L-tryptophan has several reactive groups in its molecule, consists of D- and L-amino acids, and is connected by gamma-glutamyl linkage, its chemical synthesis is complicated. An efficient enzymatic method to synthesize gamma-D-glutamyl-L-tryptophan from D-glutamine and L-tryptophan employing bacterial gamma-glutamyltranspeptidase was developed. The optimum reaction conditions were 50 mM D-glutamine, 50 mM L-tryptophan, and 0.2 U ml(-1) gamma-glutamyltranspeptidase, pH 9-9.5, and incubation at 37 degrees C for 5 h. After a 5 h incubation, 33 mM gamma-D-glutamyl-L-tryptophan was obtained, the conversion rate being 66%. The product was purified by Dowex 1 x 8 column and was considered to be gamma-D-glutamyl-L-tryptophan.

• Authors: Hideyuki Suzuki, Kenji Kato, Hidehiko Kumagai
• Journal: Journal of biotechnology (J Biotechnol) Vol. 111 Issue 3 Pg. 291-5 (Aug 05 2004) ISSN: 0168-1656 [Print] Netherlands
• PMID: 15246665 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Dipeptides
• Glutamine
• golotimod
• Tryptophan
• gamma-Glutamyltransferase

Topics

• Dipeptides (chemical synthesis, isolation & purification)
• Escherichia coli (enzymology)
• Glutamine (chemistry)
• Tryptophan (chemistry)
• gamma-Glutamyltransferase (chemistry)