N-Glycolylneuraminic acid
(Synonyms: N-羟乙酰神经氨酸,NeuGc; GcNeu) 目录号 : GC61127
A sialic acid
Cas No.:1113-83-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid that is found in non-human primate tissues.1,2 It is not endogenously produced in humans due to a mutation in the gene that encodes CMP-Neu5Ac hydroxylase, the enzyme that hydrolyzes N-acetylneuraminic acid to form Neu5Gc, but accumulates in human cells after exogenous ingestion from dietary sources such as red meat and dairy products. Neu5Gc accumulates in human tumors, including retinoblastomas, melanomas, colon carcinomas, and breast cancer, and Neu5Gc uptake is enhanced under hypoxic conditions.2
1.Nguyen, D.H., Tangvoranuntakul, P., and Varki, A.Effects of natural human antibodies against a nonhuman sialic acid that metabolically incorporates into activated and malignant immune cellsJ. Immunol.175(1)228-236(2005) 2.Hedlund, M., Padler-Karavani, V., Varki, N.M., et al.Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progressionProc. Natl. Acad. Sci. USA105(48)18936-18941(2008)
| Cas No. | 1113-83-3 | SDF | |
| 别名 | N-羟乙酰神经氨酸,NeuGc; GcNeu | ||
| Canonical SMILES | O[C@@]1(O[C@H]([C@@H]([C@H](C1)O)NC(CO)=O)[C@@H]([C@@H](CO)O)O)C(O)=O | ||
| 分子式 | C11H19NO10 | 分子量 | 325.27 |
| 溶解度 | H2O : 83.33 mg/mL (256.19 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0744 mL | 15.3718 mL | 30.7437 mL |
| 5 mM | 0.6149 mL | 3.0744 mL | 6.1487 mL |
| 10 mM | 0.3074 mL | 1.5372 mL | 3.0744 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
N-Glycolylneuraminic acid as a carbohydrate cancer biomarker
Transl Oncol 2023 May;31:101643.PMID:36805917DOI:10.1016/j.tranon.2023.101643.
One of the forms of aberrant glycosylation in human tumors is the expression of N-Glycolylneuraminic acid (Neu5Gc). The only known enzyme to biosynthesize Neu5Gc in mammals, cytidine-5'-monophosphate-N-acetylneuraminic acid (CMAH), appears to be genetically inactivated in humans. Regardless, low levels of Neu5Gc have been detected in healthy humans. Therefore, it is proposed that the presence of Neu5Gc in humans is from dietary acquisition, such as red meat. Notably, detection of elevated Neu5Gc levels has been repeatedly found in cancer tissues, cells and serum samples, thereby Neu5Gc-containing antigens may be exploited as a class of cancer biomarkers. Here we review the findings to date on using Neu5Gc-containing tumor glycoconjugates as a class of cancer biomarkers for cancer detection, surveillance, prognosis and therapeutic targets. We review the evidence that supports an emerging hypothesis of de novo Neu5Gc biosynthesis in human cancer cells as a source of Neu5Gc in human tumors, generated under certain metabolic conditions.
Current views on N-Glycolylneuraminic acid in therapeutic recombinant proteins
Trends Pharmacol Sci 2021 Nov;42(11):943-956.PMID:34544608DOI:10.1016/j.tips.2021.08.004.
The incorporation of the non-human N-Glycolylneuraminic acid (Neu5Gc) in therapeutic recombinant proteins raises clinical concerns due to its immunogenic potential and the high prevalence of pre-existing anti-Neu5Gc antibodies in humans. The scientific literature is ambiguous regarding the actual impact of Neu5Gc-containing biotherapeutics as no severe adverse clinical manifestations were unequivocally attributed to Neu5Gc for currently marketed biotherapeutics. This review discusses structural and functional considerations of Neu5Gc-containing glycans regarding the potential impact on drug clearance, their recognition by pre-existing antibodies, and recent hypotheses regarding the tolerance to low Neu5Gc levels. Furthermore, it provides recommendations regarding the standardization of analysis and reporting, analytical aspects relevant for assessing risks associated with Neu5Gc-containing biotherapeutics, and approaches to minimize Neu5Gc incorporation in recombinant protein manufacturing.
Synthesis of N-Glycolylneuraminic acid (Neu5Gc) and Its Glycosides
Front Immunol 2019 Aug 28;10:2004.PMID:31555264DOI:10.3389/fimmu.2019.02004.
Sialic acids constitute a family of negatively charged structurally diverse monosaccharides that are commonly presented on the termini of glycans in higher animals and some microorganisms. In addition to N-acetylneuraminic acid (Neu5Ac), N-glycolyl neuraminic acid (Neu5Gc) is among the most common sialic acid forms in nature. Nevertheless, unlike most animals, human cells loss the ability to synthesize Neu5Gc although Neu5Gc-containing glycoconjugates have been found on human cancer cells and in various human tissues due to dietary incorporation of Neu5Gc. Some pathogenic bacteria also produce Neu5Ac and the corresponding glycoconjugates but Neu5Gc-producing bacteria have yet to be found. In addition to Neu5Gc, more than 20 Neu5Gc derivatives have been found in non-human vertebrates. To explore the biological roles of Neu5Gc and its naturally occurring derivatives as well as the corresponding glycans and glycoconjugates, various chemical and enzymatic synthetic methods have been developed to obtain a vast array of glycosides containing Neu5Gc and/or its derivatives. Here we provide an overview on various synthetic methods that have been developed. Among these, the application of highly efficient one-pot multienzyme (OPME) sialylation systems in synthesizing compounds containing Neu5Gc and derivatives has been proven as a powerful strategy.
N-Glycolylneuraminic acid (Neu5Gc) Null Large Animals by Targeting the CMP-Neu5Gc Hydroxylase (CMAH)
Front Immunol 2019 Oct 15;10:2396.PMID:31681287DOI:10.3389/fimmu.2019.02396.
The two major sialic acids described in mammalian cells are the N-Glycolylneuraminic acid (Neu5Gc) and the N-acetylneuraminic acid (Neu5Ac). Neu5Gc synthesis starts from the N-acetylneuraminic acid (Neu5Ac) precursor modified by an hydroxylic group addition catalyzed by CMP-Neu5Ac hydroxylase enzyme (CMAH). In humans, CMAH was inactivated by a 92 bp deletion occurred 2-3 million years ago. Few other mammals do not synthetize Neu5Gc, however livestock species used for food production and as a source of biological materials for medical applications carry Neu5Gc. Trace amounts of Neu5Gc are up taken through the diet and incorporated into various tissues including epithelia and endothelia cells. Humans carry "natural," diet-induced Anti-Neu5Gc antibodies and when undertaking medical treatments or receiving transplants or devices that contain animal derived products they can cause immunological reaction affecting pharmacology, immune tolerance, and severe side effect like serum sickness disease (SSD). Neu5Gc null mice have been the main experimental model to study such phenotype. With the recent advances in genome editing, pigs and cattle KO for Neu5Gc have been generated always in association with the αGal KO. These large animals are normal and fertile and provide additional experimental models to study such mutation. Moreover, they will be the base for the development of new therapeutic applications like polyclonal IgG immunotherapy, Bioprosthetic Heart Valves, cells and tissues replacement.
Glycosylated Biotherapeutics: Immunological Effects of N-Glycolylneuraminic acid
Front Immunol 2020 Jan 23;11:21.PMID:32038661DOI:10.3389/fimmu.2020.00021.
The emerging field of biotherapeutics provides successful treatments for various diseases, yet immunogenicity and limited efficacy remain major concerns for many products. Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity. Hence, an increased attention is directed at optimizing the glycosylation properties of biotherapeutics. Currently, most biotherapeutics are produced in non-human mammalian cells in light of their ability to produce human-like glycosylation. However, most mammals produce the sialic acid N-Glycolylneuraminic acid (Neu5Gc), while humans cannot due to a specific genetic defect. Humans consume Neu5Gc in their diet from mammalian derived foods (red meat and dairy) and produce polyclonal antibodies against diverse Neu5Gc-glycans. Moreover, Neu5Gc can metabolically incorporate into human cells and become presented on surface or secreted glycans, glycoproteins, and glycolipids. Several studies in mice suggested that the combination of Neu5Gc-containing epitopes and anti-Neu5Gc antibodies could contribute to exacerbation of chronic inflammation-mediated diseases (e.g., cancer, cardiovascular diseases, and autoimmunity). This could potentially become complicated with exposure to Neu5Gc-containing biotherapeutics, bio-devices or xenografts. Indeed, Neu5Gc can be found on various approved and marketed biotherapeutics. Here, we provide a perspective review on the possible consequences of Neu5Gc glycosylation of therapeutic protein drugs due to the limited published evidence of Neu5Gc glycosylation on marketed biotherapeutics and studies on their putative effects on immunogenicity, drug efficacy, and safety.