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Carnosine conjugated hyalyronate

Cat No.:V87779 Purity: ≥98%
Carnosine conjugated hyalyronate is a hyaluronic acid derivative functionalized with the dipeptide carnosine (Car), which has the ability to resist Aβ amyloid aggregation.
Carnosine conjugated hyalyronate
Carnosine conjugated hyalyronate Chemical Structure Product category: Beta Amyloid
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
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Product Description
Carnosine conjugated hyalyronate is a hyaluronic acid derivative functionalized with the dipeptide carnosine (Car), which has the ability to resist Aβ amyloid aggregation. Carnosine conjugated hyalyronate can dissolve amyloid fibrils and reduce Aβ-induced toxicity in vitro. The anti-amyloid aggregation effect of carnosine conjugated hyalyronate is proportional to the carnosine loading.
Carnosine conjugated hyaluronate is a covalent bioconjugate of L-carnosine (beta-alanyl-L-histidine, a natural dipeptide with antioxidant properties) and hyaluronic acid (a glycosaminoglycan polymer). This conjugation enhances the antioxidant abilities and resistance to enzymatic degradation of both components, making it useful for biomedical applications such as wound healing, tissue engineering, and treating inflammatory diseases like rheumatoid arthritis and osteoarthritis.
Biological Activity I Assay Protocols (From Reference)
Targets
Carnosine conjugated hyaluronate targets reactive oxygen species (ROS) and reactive carbonyl species (RCS) due to carnosine's antioxidant activity. It also interacts with CD44 receptors (the primary receptor for hyaluronic acid) on cell surfaces, facilitating targeted delivery to sites of inflammation and tissue injury. The copper(II) complexes of this conjugate behave as superoxide dismutase (SOD) mimics, further enhancing antioxidant defense.
ln Vitro
In vitro, carnosine conjugated hyaluronate demonstrates significantly improved antioxidant properties compared to the individual components. It protects cells from oxidative stress damage, reduces inflammatory markers, and stimulates Nrf2 translocation and antioxidant response in inflammatory cell models. The conjugate also shows anti-aggregant and metal-binding abilities, contributing to its cytoprotective effects. It is not cytotoxic under normal physiological conditions.
ln Vivo
Carnosine conjugated hyaluronate has been evaluated in vivo in a traumatic skin lesion model using a carnosine and hyaluronic acid tulle (gauze dressing). The treatment showed enhanced epithelialization and wound healing properties attributed to the moisturizing, immune-modulating, anti-inflammatory, and antioxidant activities of the conjugate. Healing mechanisms involve promotion of keratinocyte migration and reduction of oxidative damage at the wound site.
Enzyme Assay
No enzyme/receptor binding assay is directly performed on the conjugate itself. Instead, antioxidant activity is measured by DPPH radical scavenging, ABTS decolorization, and FRAP assays. SOD-mimic activity is assessed by the inhibition of nitroblue tetrazolium (NBT) reduction in the presence of xanthine/xanthine oxidase. Copper(II) complexes of hyaluronate-carnosine conjugates are tested for SOD-like activity using pyrogallol autoxidation assays.
Cell Assay
Cellular assays are performed using inflammatory cell models such as RAW 264.7 macrophages or human chondrocytes. Cells are treated with the conjugate (0.1-100 microg/mL) for 12-48 h, then stimulated with LPS (lipopolysaccharide) to induce inflammation. ROS levels are measured by DCFH-DA fluorescence. Nrf2 translocation is detected by immunofluorescence microscopy. TNF-alpha, IL-6, and IL-1beta levels in the culture supernatant are measured by ELISA. Cell viability is assessed by MTT assay.
Animal Protocol
In vivo evaluation is performed in rodent models of skin wound healing. Rats or mice with full-thickness excisional wounds are treated daily with topical application of a tulle (gauze) impregnated with carnosine conjugated hyaluronate (typically 0.1-1% w/w). Wound area is measured every 2-3 days, and tissues are harvested at days 7, 14, and 21 for histological analysis (H&E staining, Masson‘s trichrome) and immunohistochemistry for CD31 (angiogenesis) and alpha-SMA (myofibroblast differentiation).
ADME/Pharmacokinetics
Carnosine conjugated hyaluronate is water-soluble due to the hyaluronic acid component. The molecular weight of hyaluronic acid used for conjugation typically ranges from 10-200 kDa, with carnosine loading of 10-30% w/w. The conjugate is stable at 4degC in PBS buffer (pH 7.4) for up to 1 month. For topical formulations, it can be incorporated into hydrogels or tulle dressings. No detailed PK parameters are available; the conjugate is expected to be localized at the application site with minimal systemic absorption.
Toxicity/Toxicokinetics
Carnosine conjugated hyaluronate is considered to have low toxicity based on its use in preclinical wound healing models and the biocompatibility of both parent compounds. No significant cytotoxicity or adverse effects have been reported at concentrations used for topical application. The compound is not for human use in its research grade. Standard laboratory safety precautions should be followed when handling the powder or solutions.
References

[1]. Hyaluronan-carnosine conjugates inhibit Aβ aggregation and toxicity. Sci Rep. 2020 Sep 29;10(1):15998.

Additional Infomation
Carnosine conjugated hyaluronate is a research-use only bioconjugate developed for biomedical applications. Carnosine (beta-alanyl-L-histidine) is a naturally occurring dipeptide found in high concentrations in muscle and brain tissues, known for its antioxidant, anti-glycating, and metal-chelating properties. Hyaluronic acid is a major component of the extracellular matrix. Their covalent conjugation is a strategy to improve the stability and efficacy of both molecules. This bioconjugate has not entered clinical trials or received regulatory approval for any indication but is being explored for wound healing and osteoarthritis therapies.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Weight
600000(Average)
Appearance
Typically exists as solid at room temperature
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

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
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Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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