Glatiramer acetate
(Synonyms: 醋酸格拉替雷) 目录号 : GC14501
醋酸格拉替雷(Glatiramer acetate,GA),也称为copolymer-1(COP-1),是一种随机混合的合成多肽,由四种氨基酸(L-谷氨酸、L-赖氨酸、L-丙氨酸和L-酪氨酸)按照残基摩尔比例4.2:3.4:1.4:1.0组成,平均分子量为4700-11000 Da。
Cas No.:147245-92-9
Sample solution is provided at 25 µL, 10mM.
Glatiramer acetate (GA), also known as copolymer-1 (COP-1), is a random mixture of synthetic polypeptides composed of four amino acids (L-glutamic acid, L-lysine, L-alanine, and L-tyrosine) in a residue molar ratio 4.2:3.4:1.4:1.0, with an average molecular mass of 4700-11,000 Da. These amino acids resemble myelin basic protein (MBP), and Glatiramer acetate has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis [1,2].
In vitro studies have shown that Glatiramer acetate competes with myelin peptides from binding to major histocompatibility (MHC) molecules and is able to displace MBP peptides from antigen presenting cells (APC) [3]. Glatiramer acetate inhibits MHC II assisted activation of myelin specific T cells [4]. Glatiramer acetate -treated (1-10 µg/ml) dendritic cells were able to shift the phenotype of naive T cells towards TH2 like T cells. In addition Glatiramer acetate inhibited the secretion of IL-12 and TNF-α by human dendritic cells and macrophages [5]. In addition to competition for binding to MHC molecules and thus inhibiting the T cell response to several myelin antigens, Glatiramer acetate is proposed to act as an antagonist to MBP/MHC at MBP-specific T cell receptors (TCR). It was demonstrated to operate as an "altered peptide ligand" to the 82-100 epitope of MBP [6].
Glatiramer acetate (250 µg/mouse, i.c.v.) and Glatiramer acetate (10, 2.5 mg/kg; s.c.) in Y-maze reversed memory impairment (LPS 100 µg/kg, i.p.). In passive-avoidance task, Glatiramer acetate (2.5, 10 mg/kg; s.c.) reversed LPS-induced impairment and the mice showed significantly longer latency times during the retention trial [7]. 2 mg/mouse of Glatiramer acetate prevented the manifestation of EAE altogether, the doses of 200 and 500 µg of Glatiramer acetate were considered suboptimal in preventing EAE, 250 µg/mouse (equivalent to 10 mg/kg) [8].
References:
[1]. Schrempf W, Ziemssen T. Glatiramer acetate: mechanisms of action in multiple sclerosis. Autoimmunity reviews. 2007 Aug 1;6(7):469-75.
[2]. Habisch HJ, SchwalenstÖcker B, Danzeisen R, Neuhaus O, Hartung HP, Ludolph A. Limited effects of glatiramer acetate in the high-copy number hSOD1-G93A mouse model of ALS. Experimental neurology. 2007 Aug 1;206(2):288-95.
[3]. Fridkis-Hareli M, Teitelbaum D, Gurevich E, Pecht I, Brautbar C, Kwon OJ, Brenner T, Arnon R, Sela M. Direct binding of myelin basic protein and synthetic copolymer 1 to class II major histocompatibility complex molecules on living antigen-presenting cells--specificity and promiscuity. Proceedings of the National Academy of Sciences. 1994 May 24;91(11):4872-6.
[4]. Gran B, Tranquill LR, Chen M, Bielekova B, Zhou W, Dhib-Jalbut S, Martin R. Mechanisms of immunomodulation by glatiramer acetate. Neurology. 2000 Dec 12;55(11):1704-14.
[5]. Vieira PL, Heystek HC, Wormmeester J, Wierenga EA, Kapsenberg ML. Glatiramer acetate (copolymer-1, copaxone) promotes Th2 cell development and increased IL-10 production through modulation of dendritic cells. The Journal of Immunology. 2003 May 1;170(9):4483-8.
[6]. Aharoni R, Teitelbaum D, Arnon R, Sela M. Copolymer 1 acts against the immunodominant epitope 82-100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking. Proceedings of the National Academy of Sciences. 1999 Jan 19;96(2):634-9.
[7]. Mohammadi F, Rahimian R, Fakhraei N, Rezayat SM, Javadi‐Paydar M, Dehpour AR, Afshari K, Ejtemaei Mehr S. Effect of glatiramer acetate on short‐term memory impairment induced by lipopolysaccharide in male mice. Fundamental & Clinical Pharmacology. 2016 Aug;30(4):347-56.
[8]. Giuliani F, Metz LM, Wilson T, Fan Y, Bar-Or A, Yong VW. Additive effect of the combination of glatiramer acetate and minocycline in a model of MS. Journal of neuroimmunology. 2005 Jan 1;158(1-2):213-21.
醋酸格拉替雷(Glatiramer acetate,GA),也称为copolymer-1(COP-1),是一种随机混合的合成多肽,由四种氨基酸(L-谷氨酸、L-赖氨酸、L-丙氨酸和L-酪氨酸)按照残基摩尔比例4.2:3.4:1.4:1.0组成,平均分子量为4700-11000 Da。这些氨基酸类似于髓鞘基础蛋白(MBP),并已经证明,醋酸格拉替雷在预防和抑制实验性自身免疫性脑脊髓炎(EAE),多发性硬化的动物模型方面非常有效[1,2]。
体外研究表明,醋酸格拉替雷可以与髓鞘肽竞争结合主要组织相容性(MHC)分子,并且能够从抗原呈递细胞(APC)中取代MBP肽[3]。醋酸格拉替雷抑制MHC II辅助激活髓鞘特异性T细胞[4]。处理醋酸格拉替雷(1-10µg/ml)的树突状细胞能够将原生T细胞的表型转变为类似于TH2的T细胞。此外,醋酸格拉替雷还抑制人类树突状细胞和巨噬细胞分泌IL-12和TNF-α [5]。除了通过竞争结合MHC分子从而抑制T细胞对多种髓鞘抗原的反应,醋酸格拉替雷还被认为在MBP特异性T细胞受体(TCR)中作为MBP/MHC的拮抗剂。它被证明是MBP 82-100表位的"改变肽配体"[6]。
醋酸格拉替雷(250 µg/只,i.c.v.)和醋酸格拉替雷(10, 2.5 mg/kg；s.c.)在Y型迷宫任务中逆转了LPS(100 µg/kg,i.p.)引起的记忆障碍。在被动避免任务中,醋酸格拉替雷(2.5,10 mg/kg；s.c.)逆转了LPS诱导的障碍,小鼠在保持试验期间显示出明显较长的潜伏期 [7]。2 mg/只的醋酸格拉替雷完全预防了EAE的表现,而200和500 µg的剂量被认为是预防EAE的亚优剂量,每只小鼠250 µg(相当于10 mg/kg)[8]。
| Cell experiment [1]: | |
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Cell lines |
THP-1 cells |
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Preparation Method |
Before starting the experiments, the cells were grown for 1 day after subculturing. Subculturing was done by harvesting the cells, resuspending in cell culture medium and culturing them at 5×105 cell/ml. Differentiation of THP-1 cells was assessed by observing adherence and cell morphology. Cells were incubated with lipopolysaccharide and where indicated, glatiramer acetate for 24 h, then the medium was removed and replaced with fresh medium containing interferon-γ. |
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Reaction Conditions |
20 µg/ml for 24 hours |
|
Applications |
Glatiramer acetate at a non-toxic concentration of 20 µg/ml inhibited tumor necrosis factor-α production by 80%, but stimulated the production of interleukin- 1β by approximately 50%. |
| Animal experiment [2]: | |
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Animal models |
LPS-induced memory impairment mice model |
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Preparation Method |
In Y-maze, Glatiramer acetate (10, 2.5, 0.625, 0.153, and 0.03 mg/kg, s.c.; 250 µg/mouse; i.c.v.) was administered 10 min following LPS, and special memory was assayed in Y-maze apparatus. In passive avoidance, LPS (100, 250 µg/kg; i.p.) was injected 4 h before receiving foot shock, and Glatiramer acetate (10, 2.5; s.c.) or (250 µg/mouse; i.c.v.) was administered 4 h before the shock. Following 24 h, the fear memory was evaluated. |
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Dosage form |
10, 2.5, 0.625, 0.153, and 0.03 mg/kg, s.c.; 250 µg/mouse; i.c.v.; 100, 250 µg/kg; i.p. |
|
Applications |
Glatiramer acetate (250 µg/mouse, i.c.v.) and Glatiramer acetate (10, 2.5 mg/kg; s.c.) in Y-maze reversed memory impairment (LPS 100 µg/kg, i.p.). In passive-avoidance task, Glatiramer acetate (2.5, 10 mg/kg; s.c.) reversed LPS-induced impairment and the mice showed significantly longer latency times during the retention trial. |
|
References: [1]: Li Q, Milo R, Panitch H, Swoveland P, Bever Jr CT. Glatiramer acetate blocks the activation of THP-1 cells by interferon-γ. European journal of pharmacology. 1998 Jan 26;342(2-3):303-10. |
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| Cas No. | 147245-92-9 | SDF | |
| 别名 | 醋酸格拉替雷 | ||
| 分子式 | (C9H11NO3.C6H14N2O2.C5H9NO4.C3H7NO2)x.xC2H4O2 | 分子量 | 4700–11,000 Da |
| 溶解度 | 33.33 mg/ml in Water (Need ultrasonic) | 储存条件 | 4°C, sealed storage, away from moisture |
| 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 | 0.2128 mL | 1.0638 mL | 2.1277 mL |
| 5 mM | 0.0426 mL | 0.2128 mL | 0.4255 mL |
| 10 mM | 0.0213 mL | 0.1064 mL | 0.2128 mL |
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| 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。
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Quality Control & SDS
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- Purity: >98.00%
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