L-Alanyl-L-Glutamine

Overview

L-glutamine (Gln) is an indispensable precursor of biosynthesis of nucleic acids, being a kind of amino acid of high abundance in the body, accounting for about 60% of whole free amino acids in the body. It is a regulator for the protein synthesis and decomposition and is the carrier for the transportation of amino acids from peripheral tissue to internal organs, being an important matrix for renal excretion. It plays an important effect on the immune function and lesion repair of the body. However, L-glutamine has limited application in the parental nutrition due to its low solubility, being unstable in aqueous solution, incapable of tolerating heat sterilization and easily releasing toxic substances upon heating. L-alanyl-L-glutamine (Ala-Gln) dipeptide is widely used as the application vector of Gln in clinical practice.
L-alanyl-L-glutamine is stable, highly soluble and thermal and sterilization resistant. After entering into the body, it can be quickly digested into L-glutamine to exert its effect. It has high bioavailability and wide range of applications, thus making up the deficiency of the L-glutamine with particularly important effects for patients with sudden trauma. At harsh time, L-alanyl-L-glutamine plays an important role in enhancing the fighting capability of soldiers. Moreover, its application in parenteral nutrition has also drawn more and more attention. At present, the vast majority of domestic L-alanyl-L-glutamate depends on imports. Therefore, in harsh time, we will face a situation of no drug. Therefore its market prospect is limitless.
L-Alanyl-L-Glutamine (Ala-Gln), its 20% intravenous injection is developed and produced by the German F resenius AG. In April 1995, it was registered and listed in Germany under the name of Dipeptamin, being registered in China in 1999 under the trade name of 20% Dipeptamin. L-Alanyl-L-Glutamine has been used as a clinical donor, being drugs for parenteral nutrition, like saline and glucose as a necessity for ambulance patients with its market prospects being limitless.
L-alanyl-L-glutamine is a chemically synthesized dipeptide which is degraded into L-glutamine and L-alanine in vivo for substance synthesis or energy consumption inside the body. The drug has excellent therapeutic efficacy on treating severe catabolic diseases such as major burn injury, acute and chronic infection, bone marrow transplantation and multiple organ dysfunction syndrome, intestinal dysfunction such as enteritis short bowel syndrome and radiotherapy and chemotherapy-induced mucosal injury, immunodeficiency syndrome such as AIDS, critical illness or the concurrent immune dysfunction after bone marrow transplantation with relative extensive clinical application.

Property

This product appears as white or almost white crystalline powder, being odorless; has hygroscopicity; being easily soluble in water, almost insoluble in the methanol and only slightly soluble in glacial acetic acid.

Pharmacological effects

This product is an integral part of parenteral nutrition, N (2)-L-alanyl-L-glutamine can be broken down into glutamine and alanine in the body. Its characteristics is that it can supplement glutamine through parenteral nutrition infusion; The released amino acids of this kinds of dipeptide can be stored in the corresponding parts of the body as a nutrient and metabolized in response to the demands of the body. For symptoms that can possibly cause in vivo glutamine depletion, the goods can be supplemented for parenteral nutrition support.

Pharmacokinetics

N (2)-L-alanyl-L-glutamine is subject to rapid decomposition into glutamine and alanine in vivo with its human half-life of 2.4 to 3.8 minutes (being 4.2 minutes for late renal dysfunction patients), and the plasma elimination rate was 1.6 to 2.7 L/min. The disappearance of this dipeptide is accompanied by an increase in the number of free amino acids of equal molar number. Its hydrolysis process may only occur in the extracellular. When the infusion volume is constant, N (2)-L-alanyl-L-glutamine excreted through the urine is less than 5%, being identical to the other infused amino acids.

Uses

This product is an integral part of parenteral nutrition and is indicated for patients who require supplementation with glutamine, including those in catabolic and metabolic conditions. Such as: trauma, burns, large and medium-sized operation, bone marrow and other organ transplantation, gastrointestinal syndrome, cancer, severe infection and other stressful ICU patients. This product is a supplement to the amino acid solution. Upon application, it should be supplemented into other amino acid solution or infusion containing amino acids.
It is a kind of dipeptide used as the glutamine substituents in mammalian cell culture media; glutamine is unstable in solution with the formed ammonia having deleterious effects in cell culture; Ala-Glu is stable against thermal disinfection, having a smaller effect of ammonia formation than glutamine. As one of the components of the medium, it is advantageous to exert its advantages

Description

L-Alanyl-L-glutamine is a synthetic glutamine dipeptide that can attenuate oxidative stress in rodent models when administered at doses of 0.75-1.5 mg/kg. In vivo, the parenteral administration of L-alanyl-L-glutamine to Swiss mice yields higher plasma glutamine levels compared to enteral administration. In vitro, the addition of this dipeptide (50 mM) to cultures of antibody-producing CHO cells reduces apoptosis and promotes antibody production. Treatment of insulin-secreting BRIN-BD11 β-cells with L-alanyl-L-glutamine (2 mM) protects against the inflammatory effects of exposure to lipopolysaccharide-treated primary macrophages.

Chemical Properties

White Solid

Uses

A substitute for glutamine in mammalian cell culture media; stable to heat-sterilization.L-Alanyl-L-glutamine is used as a component in pharmaceuticals, cosmetics and food products. It is a stable Gln dipeptide, which protects mice against the jejunal crypt depletion in the setting of dietary protein and fat deficiency. It provides nutritional requirements, improves intestinal health and enhances the immune system. It is also involved in various clinical studies such as cancer treatment, radiation and chemotherapy. It finds application in biotechnology as a component for mammalian cell culture medium. It improves pancreatic beta-cell function, maintaining the mitochondrial metabolism and stimulus-secretion coupling essential for insulin release.

Uses

This supplement provides a stable form of L-glutamine while in solution.

Uses

Ala-Gln has been used:

• as a supplement in NeuralQmedium
• as a component in growth medium and incubation medium (IM) for retinal cell lines
• for experimental treatment of retinal cell lines respectively

Definition

ChEBI: A dipeptide formed from L-alanyl and L-glutamine residues.

Biochem/physiol Actions

Alanyl-glutamine is a widely used alternative supplement to L-glutamine in the production of biopharmaceuticals. Alanyl-glutamine also acts as an antioxidant (peroxide) and anti-apoptosis (LPS-induced) factor. Ala-Gln has been used in studies on injury and sepsis, and on the effects of irradiation on leucine and protein metabolism in vivo. Ala-Gln has been utilized to investigate polymorphonuclear leucocyte and myeloperoxidase activity in vitro.

Synthesis

56-85-9

1142-20-7

39537-23-0

1. Prepare a solution of triphenylphosphine by dissolving 15 mmol of triphenylphosphine in 10 mL of tetrahydrofuran. 2. in another vessel, a mixed system was prepared by mixing 10 mmol of benzyloxycarbonyl-L-alanine (Z-Ala) with 20 mmol of hexachloroethane in 10 ml of tetrahydrofuran. 3. Triphenylphosphine solution was slowly added dropwise to the above mixed system, keeping the reaction temperature at 0°C and the reaction time at 1.5 hours. 4. The reacted mixture was added dropwise to a liquid mixture containing 18 mmol of L-glutamine, 20 ml of water and 40 ml of dichloromethane. 5. During the dropwise addition, the pH of the reaction system was adjusted to 13 using potassium hydroxide solution, the reaction temperature was maintained at 0°C, and the reaction was continued for 2 hours after completion of the dropwise addition. 6. After completion of the reaction, the reaction solution was acidified to pH=2.0 using dilute sulfuric acid. 7. Concentrate the reaction solution and separate the aqueous phase. 8. 8. React the aqueous phase with hydrogen in methanol at room temperature for 15 hours to carry out the hydrogenation reaction. 9. Upon completion of the reaction, the target product L-alanyl-L-glutamine was obtained in 65% yield.

References

[1] Patent: US2005/233977, 2005, A1. Location in patent: Page/Page column 4-5
[2] Patent: US2005/233977, 2005, A1. Location in patent: Page/Page column 4
[3] Patent: US2005/233977, 2005, A1. Location in patent: Page/Page column 5