What is the function of 99% purity 6-Diazo-5-Oxo-L-Norleucine?
Product overview and key physical and chemical properties
99% purity 6-Diazo-5-Oxo-L-Norleucine is a natural product from Streptomyces, which belongs to a diazone derivative of non-protein ogenic L-α- amino acid. Its chemical formula is C6H9N3O3, its molecular weight is 171.15, and its CAS number is 157-03-9. Its structural feature is that the oxo group is introduced into the C-5 position of L-Norleucine and the diazo group is introduced into the C-6 position, forming a typical α-amino acid-diazone structure, which endows it with the potential to inhibit a variety of enzymes related to metholone metabolism.
Key physical and chemical properties and storage points
Appearance and properties: DON is a light yellow crystalline powder, which is sensitive to light and moisture. It is recommended to operate it in the dark, dry and low temperature. Its melting point is about 145°C, and its solubility in water is relatively high (about 34 mg/mL, 25°C). It is suggested that the prepared aqueous solution should be used now, and mild heating and ultrasonic-assisted dissolution can be combined if necessary.
Stability and storage: Long-term storage (powder) at-20 C is recommended, and the prepared solution is generally stored at 2–8 C for a short time to avoid repeated freezing and thawing; Wear gloves, goggles and protective masks during operation, avoid inhaling dust/aerosol, and follow good laboratory specifications.
99% purity 6-Diazo-5-Oxo-L-Norleucine's "super power": how does it work?
"Traffic Police" of Glutamine Metabolism
To understand its function, we must first know Boc-D-Glutamine. Boc-D-Glutamine is an important amino acid in human body, just like "fuel" and "building material" in cells. Many cells, especially rapidly proliferating cells (such as cancer cells), especially rely on Boc-D-Glutamine to obtain energy and synthesize new substances.
It's like a "traffic policeman", setting up a card at every intersection of its metabolism to prevent Boc-D-Glutamine from being used normally. It mainly targets at those enzymes that need Boc-D-Glutamine as raw material, and makes these enzymes "strike".
"target" of attack
Its attack range is very wide, and it mainly aims at the following key "targets":
1）GLUTAMINASE
This enzyme is responsible for decomposing Boc-D-Glutamine into L-Glutamic acid, which can be converted into other important substances. 99% purity 6-Diazo-5-Oxo-L-Norleucine inhibits this enzyme, which is equivalent to cutting off an important way for cells to obtain energy and raw materials.
2) Purine and pyrimidine synthetases
Purine and pyrimidine are the basic units of DNA and RNA, just like bricks for building a house. These enzymes need Boc-D-Glutamine to synthesize purine and pyrimidine. It stops these enzymes, so cells can't synthesize new DNA and RNA, so they can't divide and proliferate.
3) NAD synthase
NAD is an important coenzyme of energy metabolism in cells, which provides energy for various biochemical reactions just like batteries. When it inhibits the synthesis of NAD, cells will be "cut off" and all kinds of life activities will be affected. Why are cancer cells particularly afraid of 6-Diazo-5-Oxo-L-Norleucine? Cancer cells grow very fast and need a lot of energy and raw materials. Their dependence on Boc-D-Glutamine is much higher than that of normal cells, which is called "glutamine addiction". DON specifically targets the metabolism of Boc-D-Glutamine, so it has a particularly strong killing effect on cancer cells, but has a relatively small impact on normal cells. This is like giving cancer cells "no food and no water" and letting them "starve" alive.
The application of DON in scientific research and medical treatment
"Universal tool" in scientific research
In the laboratory, DON is the "star molecule" to study metabolism. Scientists use it to:
1) study tumor metabolism
By adding 6-Diazo-5-Oxo-L-Norleucine to cancer cells and observing the changes of cell growth, energy metabolism and invasion and metastasis ability, we can reveal the role of Boc-D-Glutamine metabolism in tumor occurrence and development.
2) study the function of immune cells
Immune cells (such as T cells and macrophages) also need a lot of Boc-D-Glutamine when activated. Treating immune cells with DON can study how metabolism affects immune response.
3) study tissue regeneration
When repairing tissue injury, cells need to proliferate rapidly and also rely on Boc-D-Glutamine. DON can help scientists understand the metabolic mechanism of tissue regeneration.
"candidates" for anti-tumor products
Although DON itself can't be directly used in clinic because of its toxicity, scientists are "upgrading" it and developing various prodrugs.
Prodrugs are like putting an "invisibility cloak" on DON, so that it will not be recognized after entering the body, and only when it reaches the tumor site will it "take off the invisibility cloak" and release active DON. This can not only kill cancer cells, but also reduce the damage to normal tissues.
Other potential applications
In addition to anti-tumor, 99% purity 6-Diazo-5-Oxo-L-Norleucine also has research value in the following fields:
) 1 Inflammatory diseases
In some inflammatory diseases (such as rheumatoid arthritis and psoriasis), immune cells are over-activated, which requires a lot of Boc-D-Glutamine. DON may reduce the inflammatory reaction by inhibiting the metabolism of immune cells.
2) Fibrosis disease
In diseases such as pulmonary fibrosis and liver fibrosis, fibroblasts proliferate excessively and produce too much collagen. DON may delay the process of fibrosis by inhibiting the proliferation of these cells.
3) nervous system diseases
DON may be used to study the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
6-Diazo-5-Oxo-L-Norleucine's "advantages and disadvantages"
advantage
1) The mechanism of action is clear
99% purity 6-Diazo-5-Oxo-L-Norleucine has a clear target and a relatively clear mechanism, which is easy to study.
2) broad-spectrum inhibition
DON can inhibit several Boc-D-Glutamine-dependent enzymes at the same time, resulting in synergistic effect.
3) Mature research tools
6-Diazo-5-Oxo-L-Norleucine has been used as a research tool for many years, with mature experimental methods and good data repeatability.
4) Great development potential
Through the transformation of pre-drug, it is expected to overcome the unfavorable factors and realize clinical application.
disadvantage
The selectivity is not enough. Although cancer cells are more dependent on Boc-D-Glutamine, DON also affects the metabolism of normal cells.
conclusion
Although the name of 6-Diazo-5-oxo-L-norleucine(DON) is complicated, it is a very valuable scientific research tool. It was isolated from Streptomyces and became a "star molecule" to study metabolism. We should make full use of DON to explore the role of Boc-D-Glutamine metabolism in diseases, and at the same time, we should pay attention to safe use and standardized operation. In the future, with the progress of prodrug technology and the optimization of combination therapy strategy, DON and its derivatives are expected to bring new hope for the treatment of tumors and other diseases.
Xi'an Faithful BioTech Co., Ltd. combines cutting-edge production technology with comprehensive quality assurance to provide high-quality 99% purity 6-Diazo-5-Oxo-L-Norleucine that meets international pharmaceutical standards. Our commitment to excellent, competitive prices and technical support makes us the preferred partner of global healthcare providers and researchers. Please contact our technical team in sales11@faithfulbio.com to find out how our products can improve your formula.
This is a list of the names of the core scientific research documents that I referred to and relied on in the process of writing a soft article. These documents provide solid scientific evidence for the efficacy and mechanism mentioned in this paper.
- "Synthesis of 6-Diazo-5-oxo-L-norleucine" by DeWald & Moor, J. Am. Chem. Soc., 1958
- "The Structure of DON" by Dion et al., J. Am. Chem. Soc., 1956
- "Glutamine Antagonists in Cancer Therapy" by Ahluwalia et al., Cancer Res., 1990
- "Metabolic Reprogramming by DON" by Wise et al., Proc. Natl. Acad. Sci., 2008
- "DON inhibits glutaminase and glutamine-dependent enzymes" by Pinkus, Methods Enzymol., 1977
- "DON sensitizes pancreatic cancer to immunotherapy" by Leone et al., Nature, 2019
- "DON and γδ T cell function" in IL-17A production studies
- "DON in glioma metabolism" by various authors
- "NQO1-activated DON prodrugs" in CN113461563B
- "Antibody-drug conjugates with DON" in US2018267067A1
- "LC-MS/MS methods for DON quantification" in US2018267067A1
