Development of an efficient enzymatic production of γ- d-glutamyl- l-tryptophan (SCV-07), a prospective medicine for tuberculosis, with bacterial γ-glutamyltranspeptidase

Abstract

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