| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Dipeptidyl peptidase-IV (DPP-IV)
The primary biological target of D-gamma-Glu-Tyr is dipeptidyl peptidase-IV (DPP-IV, also known as CD26), a serine exopeptidase. D-gamma-Glu-Tyr is a D-isomer analog of the competitive DPP-IV inhibitor gamma-Glu-Tyr. The parent peptide, gamma-Glu-Tyr, competitively inhibits DPP-IV. DPP-IV is responsible for the rapid degradation of incretin hormones like GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide), which play a crucial role in glucose homeostasis. By inhibiting DPP-IV, these incretin levels can be increased. |
|---|---|
| ln Vitro |
DPP-IV inhibitory activity: In a fluorometric enzyme assay, γ-Glu-Tyr exhibited competitive inhibition against dipeptidyl peptidase-IV (DPP-IV) with an IC₅₀ value of 6.77 ± 0.68 mM. Lineweaver-Burk plot analysis confirmed that the inhibition was competitive, with no significant change in Vₘₐₓ in the presence of the inhibitor, while Kₘ increased. [1]
Comparison with other γ-glutamyl dipeptides: Among the 20 tested γ-glutamyl dipeptides, only five (γ-Glu-Met, γ-Glu-Leu, γ-Glu-Phe, γ-Glu-Trp, and γ-Glu-Tyr) exhibited DPP-IV inhibitory activity with IC₅₀ values below 10 mM. γ-Glu-Tyr showed the highest IC₅₀ among these five active peptides, indicating the weakest inhibitory potency. [1]
The in vitro activity of D-gamma-Glu-Tyr is inferred from its parent compound, gamma-Glu-Tyr. Studies have shown that gamma-Glu-Tyr is a competitive inhibitor of dipeptidyl peptidase-IV (DPP-IV) with an IC50 of 6.77 mM. The IC50 value indicates the half-maximal inhibitory concentration of the peptide against the enzyme. This relatively high IC50 (in the millimolar range) suggests it is a weak inhibitor compared to synthetic pharmaceuticals, but its presence as a dietary component may contribute to glycemic control when consumed in large amounts. |
| ln Vivo |
Specific in vivo activity data for D-gamma-Glu-Tyr are not reported. However, its parent compound gamma-Glu-Tyr has been studied as a potential functional component of the diet for type 2 diabetes management. The rationale is that consuming DPP-IV inhibitory peptides could increase endogenous GLP-1 levels, thereby improving insulin secretion and lowering blood glucose in a nutrient-dependent manner. This effect would be most pronounced postprandially (after a meal) and may be milder than pharmaceutical DPP-IV inhibitors like sitagliptin.
|
| Enzyme Assay |
DPP-IV inhibition assay: The DPP-IV inhibitory activity was measured using a fluorometric DPP-IV inhibitor screening kit. Assays were performed in black-walled 96-well plates with DPP-IV assay buffer (20 mM Tris-HCl, pH 8.0, containing 100 mM NaCl and 1 mM EDTA). γ-Glu-Tyr was dissolved in HPLC-grade water at concentrations ranging from 0.0125 to 2.5 mg/mL. The fluorescence change at 360/460 nm was monitored at 2-minute intervals over 30 minutes using a microplate reader. Initial slopes in the absence or presence of the test sample were used to calculate inhibitory activity. Sitagliptin was used as a positive control. IC₅₀ values were calculated by logarithmic regression analysis. [1]
Kinetic analysis of inhibition: The inhibition kinetics of γ-Glu-Tyr were evaluated using Lineweaver-Burk plots. The affinity constant (Kₘ without inhibitor), apparent affinity constant (Kₐₚₚ with inhibitor), and maximum reaction rate (Vₘₐₓ) were determined from double reciprocal plots. Competitive inhibition was confirmed by the finding that Vₘₐₓ remained unchanged while the slope and x-intercept changed in the presence of the inhibitor. [1]
A standard protocol for a non-cellular (in vitro enzyme) assay for D-gamma-Glu-Tyr involves a DPP-IV Inhibition Assay. The assay buffer contains 100 mM Tris-HCl (pH 8.0). The test compound (D-gamma-Glu-Tyr) is serially diluted and added to a 96-well plate. Purified human DPP-IV enzyme is added, followed by a fluorogenic substrate, H-Gly-Pro-AMC (7-amino-4-methylcoumarin). The reaction is incubated at 37degC for 30 minutes. The fluorescence is measured with a microplate reader at an excitation of 360 nm and an emission of 460 nm. The IC50 is calculated by comparing fluorescence units to a control. |
| Cell Assay |
To confirm the cellular activity of a DPP-IV inhibitor, an in vitro cell-based assay can be used with Caco-2 cells (human colorectal adenocarcinoma) that endogenously express DPP-IV on their surface. The cells are cultured in a 24-well plate in DMEM medium until confluent. The cells are washed and incubated with the test compound, D-gamma-Glu-Tyr, for 30 minutes at 37degC. A synthetic substrate (Gly-Pro-pNA) is added, and the production of p-nitroaniline is measured spectrophotometrically at 405 nm. The decrease in optical density indicates DPP-IV inhibition on the cell surface.
|
| Animal Protocol |
In vivo animal experiments for DPP-IV inhibitors typically use a rodent model of type 2 diabetes, such as db/db mice or high-fat diet (HFD)-fed mice. A standard protocol involves orally administering D-gamma-Glu-Tyr (e.g., 50-300 mg/kg) daily for 2-4 weeks. Primary endpoints include: 1) Oral glucose tolerance test (OGTT) to measure blood glucose levels at 0, 30, 60, 90, and 120 minutes after glucose load, and 2) Measurement of active GLP-1 levels in plasma using an ELISA kit.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for D-gamma-Glu-Tyr are not available in the provided references. As a dipeptide, it would likely be susceptible to rapid hydrolysis by peptidases in the gastrointestinal tract and plasma, leading to a very short half-life. However, the D-isomer configuration of glutamic acid may increase its stability against proteolytic degradation compared to the L-isomer. Systemic absorption is likely limited unless specialized peptide delivery systems are used.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for D-gamma-Glu-Tyr are not provided. The compound is a structural variant of a dipeptide naturally found in some fermented foods. Therefore, it is expected to have a low toxicity profile, consistent with being a potential "functional component of the type 2 diabetes diet." As it is derived from amino acids, it is likely metabolized to harmless components. However, as with any research chemical, handling precautions should be followed.
|
| References | |
| Additional Infomation |
D-gamma-Glu-Tyr is not a clinically approved drug. It is a research chemical used to explore the therapeutic potential of naturally occurring DPP-IV inhibitors. This compound represents a "nutraceutical" approach to managing type 2 diabetes, contrasting with the "pharmaceutical" approach of synthetic drugs like vildagliptin. It serves as a lead compound for developing improved peptide-based DPP-IV inhibitors with better stability and oral bioavailability. The presence of a D-amino acid in the sequence is a key modification to study proteolytic stability in peptide drug design. Gamma-glutamyl peptides are also associated with kokumi taste in foods, implicating this compound in sensory research. While D-Glu-Tyr has not been tested in humans, the parent gamma-Glu-Tyr has been investigated for its potential to lower postprandial blood glucose.
|
| Molecular Formula |
C14H18N2O6
|
|---|---|
| Molecular Weight |
310.30
|
| CAS # |
2417507-97-0
|
| Related CAS # |
γ-Glu-Tyr; 7432-23-7
|
| Sequence |
{D-γ-Glu}-Tyr{D-γ-Glu}-Y
|
| Appearance |
Solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : ~12.5 mg/mL (~40.28 mM; ultrasonic and adjust pH to 8 with NH3·H2O)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2227 mL | 16.1134 mL | 32.2269 mL | |
| 5 mM | 0.6445 mL | 3.2227 mL | 6.4454 mL | |
| 10 mM | 0.3223 mL | 1.6113 mL | 3.2227 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
