GGsTopTM

GGT, which is also known as γ-GT (γ-glutamyltransferase) or γ-GTP (γ-glutamyl transpeptidase) is a cell membrane-bound enzyme that hydrolyzes the γ-glutamyl bond between the Glu and Cys-Gly of glutathione (γ-Glu-Cys-Gly). GGT is a key enzyme in glutathione metabolism, as well as affecting intracellular glutathione levels, and it is thought to be involved in many diseases such as cardiovascular disease, type 2 diabetes mellitus, and the resistance of cancer cells to chemotherapeutic agents.

GGsTop^® is a highly selective GGT inhibitor. Acivicin (AT-125), which has been widely used as a GGT inhibitor, inhibits glutamine amidotransferase (GA family) in addition to GGT, while GGsTop^® shows high specificity for GGT without showing inhibitory activity against the GA family. It has also been reported to promote the production of collagen and elastin, and is being applied in the field of cosmetics.

• Highly specific to GGT
• High inhibitory activity for human GGT
• Low toxicity
• Chemically stable

Inhibitory activity against human and E. coli GGTs

k_on: second order rate constant for enzyme inhibition (inactivation)

Inhibitory activity against asparagine synthetase

Dissolution stability

Stable for at least 1 month at room temperature in neutral water or acidic aqueous solution (e.g. :0.1% TFA solution and 0.1 N HCl solution). Avoid dissolving this product in alkaline solution (pH 9 or higher) due to the consequent instability.

Usage

Dissolve this product in distilled water to prepare a 10 mmol/L stock solution, divide into small aliquots, and store at -20°C. Avoid repeated freeze-thaw cycling of the stock solution.

Storage conditions

Store at -20°C.
As this product is highly hygroscopic, immediately stopper or seal the container after use. If moisture is absorbed, it can be used without problems after drying in a desiccator under vacuum, using a desiccant such as diphosphorus pentoxide.

1. Han, L. et al. : Biochemistry, 46, 1432 (2007). Design, Synthesis, and Evaluation of γ-Phosphono Diester Analogues of Glutamate as Highly Potent Inhibitors and Active Site Probes of γ-Glutamyl Transpeptidase
2. Hiratake J.：和光純薬時報, 76(3), 2 (2008). (Japanese)
3. Yamamoto, S. et al. : J. Pharmacol. Exp. Ther., 339, 945 (2011). Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats
4. Brady, M. J. et al. : Current Enzyme Inhibition, 7, 71 (2011). Inhibiting Glutathione Metabolism in Lung Lining Fluid as a Strategy to Augment Antioxidant Defense
5. Yuasa, A., et al. : Journal of Japanese Cosmetic Science Society, 36(2), 93 (2012). A γ-Glutamyl Transpeptidase (GGT) Inhibitor Enhances Collagen and Elastin Synthesis (Japanese)
6. Kubota, R. et al. : Br. J. Pahrmacol., 177(22), 5195 (2020). Inhibition of γ-glutamyltransferase ameliorates ischaemia-reoxygenation tissue damage in rats with hepatic steatosis
7. Ichikawa, S et al. : Int. J. Oral-Med. Sci., 18(3)(4), 183 (2020). A GGT Inhibitor Suppresses IL-6 and IL-8 Expressions Enhanced by LPS in Gingival Fibroblasts
8. Jiang, Y. et al. : Mol. Med. Rep., 13(5), 3813 (2016). GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway
9. Terzyan, S. S. et al. : J. Biol. Chem., 290(28), 17576 (2015). Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS
10. Sakuma, K., et al. : Journal of the Japanese Society for Disability and Oral Health, 41(1), 1 (2020). The effect of γ-glutamyl transpeptidase inhibitor on wound healing of oral mucosa (Japanese)
11. 11.Baumann, T. et al. : Exp. Dermatol., 23(4), 247 (2014). Glutathione-conjugated sulfanylalkanols are substrates for ABCC11 and γ-glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland
12. Mizushima, T. et al. : BMC Cancer, 16, 411 (2016). Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study
13. Tobe, T. et al. : J. Toxicol. Sci., 42(1), 85 (2017). Selenium uptake through cystine transporter mediated by glutathione conjugation
14. Kubo, H. et al. : Sci. Rep., 8, 17781 (2018). Rapid detection of metastatic lymph nodes of colorectal cancer with a gamma-glutamyl transpeptidase-activatable fluorescence probe
15. Akashi, T. et al. : Sci. Rep., 9, 9467 (2019). A novel method for rapid detection of a Helicobacter pylori infection using a γ-glutamyltranspeptidase-activatable fluorescent probe