Highly Selective
γ-Glutamyl transpeptidase (GGT) Inhibitor
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GGT, which is also known as GTP, GPT, γ-GTP, γ-GT, γ-GPT, γ- glutamyltransferase, γ-glutamyl
transpeptidase or γ-glutamyl peptidyltransferase (EC 2.3.2.2) is a cell membrane-bound enzyme that
hydrolyzes γ-glutamyl bond between Cys and Gly of glutathione (γ-Glu-Cys-Gly).
GGT is involved in a number of biological events such as drug resistance and metastasis of cancer cells
by detoxification of xenobiotics and reactive oxygen species through glutathione metabolism, and is
also implicated in physiological disorders, such as Parkinson’s disease, neurodegerative disease, Type
II diabetes and cardiovascular diseases.
GGsTop™ is a highly selective γ-Glutamyl Transpeptidase (GGT) inhibitor. While acivicin
[AT-125], which has been widely used as a GGT inhibitor also inhibits asparagine synthetase (GA
family); GGsTop™ does not inhibit the asparagine synthetase.
GGsTop™ shows 100 times higher inhibitory activity toward human GGT than that of acivicin. It is a
very useful tool for GGT research.
Features
1. High specificity to GGT
2. High inhibitory activity to human GGT
3. Low toxicity
On acute toxicity test, there is no toxicity with intravenously
infused GGsTop™ (30 mg/kg).
On the other hand, acivicin has severe toxicity to the CNS.
4. Chemically stable
Inhibitory Activity toward human and E. coli GGT
High Inhibitory Activity of GGsTop™
GGsTop™
Acivicin [AT-125]
Kon(M-1s-1)
to human GGT
to E. coli
51
170
0.40
4,200
Kon: second-order rate constant for enzyme inactivation
GGsTop™ exhibited approximately 100 times
higher inhibitory activity toward human GGT
than that of acivicin.
Inhibitory Activity toward E. coli Asparagine Synthesis Enzyme
GGsTop™
Acivicin [AT-125]
Inhibition Concentration
> 10 mmol/L (does not exhibit inhibitory activity for asparagine synthesis enzyme)
100 µmol/L (exhibits deactivation of 90+ % of asparagine synthesis enzyme after 2 hours)
High Specificity of GGsTop™
Inhibitory activity toward E. coli Asparagine Synthesis
Enzyme of GGsTop™ and Acivicin was measured,
respectively. GGsTop™ did not show inhibitory activity
even at the 100 times concentration of Acivicin [AT-125].
These results showed GGsTop™ to be a highly specific inhibitor to GGT.
Reconstitution
Dissolve this product in distilled water to make 10 mmol/L stock solution. Please keep the stock solution at
-20 ºC after aliquoting in appropriate number. Avoid freezing and thawing of the stock solution.
Stability after reconstitution
The reconstituted neutral or acid aqueous solution
such as 0.1 % TFA solution and 0.1 N HCl solution is
stable for 1 month at room temperature.
Avoid reconstituting GGsTop™ with alkaline solution
(> pH 9) due to the instability.
Chemically Stable of GGsTop™
Storage
Keep at -20 ºC
* Recap immediately after use because it is highly hygroscopic. When GGsTop™ absorbs moisture, vacuum-dry it in a desiccator
with an appropriate desiccant such as Diphosphorus Pentaoxide.
Reference
Han, L., Hiratake, J., Kamiyama, A. and Sakata, K.: “Design, synthesis, and evaluation of γ-phosphono diester
analogues of glutamate as highly potent inhibitors and active site probes of γ-glutamyl transpeptidase”
Biochemistry, 46, 1432-47(2007).
Description
Wako Catalog No. (Pkg. Size)
Note
GGsTop™
for Cellbiology
075-05471 (10’ mg)
(2-Amino-4-{[3-(carboxymethyl)phenyl]
(methyl)phosphono} butanoic Acid)
CAS No. 926281-37-0
C13H18NO7P = 331.26
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