Biological Activity
ou749 is a competitive inhibitor of γ-glutamyl transpeptidase (ggt) [1].expression of γ-glutamyl transpeptidase (ggt) in tumors contributes to the resistance to radiation and chemotherapy. ggt is inhibited by glutamine analogues which compete with the substrate for the γ-glutamyl binding site [1].ou749 inhibited human kidney ggt with an intrinsic ki of 17.6 m [1]. in 786-o cells, a human renal tumor cell line, ou749 showed more than 150-fold less toxic than the ggt inhibitor acivicin toward dividing cells. ou749 inhibited ggt isolated from human kidney in a dose-dependent manner [1]. ou749 was 7-fold less potent as inhibitor of ggt isolated from rat kidney and 10-fold less potent inhibiting ggt from mouse kidney [1]. ou749 did not inhibit degradation of glutathione by ggt from rat kidney. inhibition of ggt by ou749 is species-specific [1]. ou749 showed no inhibitory effect on ggt from pig cells. ou749 inhibited human ggt expressed in mouse fibroblasts by a similar extent to the ggt from human cells, indicated that the species specificity was determined by differences in the primary structure of the protein rather than species-specific, post-translational modifications [1].
References
[1] king j b, west m b, cook p f, et al. a novel, species-specific class of uncompetitive inhibitors of γ-glutamyl transpeptidase[j]. journal of biological chemistry, 2009, 284(14): 9059-9065.
