N,S-Bis-Fmoc-glutathione

N,S-Bis-Fmoc-glutathione(DiFMOC-G) which has been synthesized and characterized is a very potent competitive inhibitor of mammalian glyoxalase II activity(K, =0.75 M, calfliver glyoxalase II). Among other enzymes involved in glutathione metabolism, such as glutathione S-transferase, glutathione reductase, and glutathione peroxidase, only glutathione S-transferase is inhibited to a small extent by N,S-Bis-Fmoc-glutathione ^[2]. The thiocarbonate derivatives of glutathione, which bind very strongly to glyoxalase II and serve as effective competitive inhibitors of the enzyme, also serve as weak substrates for glyoxalase II^[1].For example, the KM values for p-NCB-G and for N,S-Bis-Fmoc-glutathione are 4 µM and 1.5 µM, respectively, when tested with pure calf-liver glyoxalase II.The relative V,max.values, compared with the V,max.with SLG as substrate, are 0.125% and 0.45%, for pNCB-G and N,S-Bis-Fmoc-glutathione, respectively^[1].

Embryonic neural cells undergo rather major elaborations of network connections within a few days of culturing in vitro. These networks, resulting from the extension of processes elaborated by the cells, require extensive synthesis ofamicrotubularcytoskeleton ^[3]. These neurons show profound effects from the N,S-Bis-Fmoc-glutathione diester treatment; extending neurites have contracted or disappeared and the cells, in some cases, have begun to disintegrate. After 47-72 h exposure to the N,S-Bis-Fmoc-glutathione diester, all identifiable cells have become globular in shape^[2].

References:
[1]: Norton SJ, Elia AC, et,al. Inhibitors and inhibition studies of mammalian glyoxalase II activity. Biochem Soc Trans. 1993 May;21(2):545-9. doi: 10.1042/bst0210545. PMID: 8359529.
[2]:EliaAC,ChyanMK,et,al.N,S-bis-fluorenylmethoxycarbonylglutathione: a new, very potent inhibitor of mammalian glyoxalase II. Biochem Mol Biol Int. 1995 Apr;35(4):763-71. PMID: 7627127.
[3]: Alberts, B., Bray, D. et,al. (2014). Essential Cell Biolog (4th ed.). W.W. Norton & Company. https://doi.org/10.1201/9781315815015