Larazotide acetate
(Synonyms: 醋酸拉瑞唑来) 目录号 : GC33822
Larazotide acetate（以前称为 AT-001）是一种高度极性的八肽，来源于霍乱弧菌分泌的原核闭合带蛋白。
Cas No.:881851-50-9
Sample solution is provided at 25 µL, 10mM.
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Larazotide acetate (formerly AT-001) is a highly polar octapeptide, derived from a prokaryotic zonula occludens protein secreted by Vibrio cholera[6].
In vitro studies have shown larazotide acetate can prevent the opening of tight junctions, induced by cytokines, bacterial agents and gluten fragments[7,8]. In Lucifer yellow (LY) permeability assays, AT-1002 induces TJ barrier dysfunction in human-derived Caco-2 cells[2], AT-1002 caused a substantial increase in LY passage, which was inhibited by larazotide acetate in a dose-dependent manner. Larazotide acetate at 15 and 12.5 mM significantly inhibited the AT-1002-induced increase in LY passage by 71 and 38%, respectively[1]. Larazotide acetate inhibits gliadin-induced cytoskeletal reorganization in IEC-6 cells[3].
In vivo in gliadin-sensitized HLA-HCD4/DQ8 double transgenic mice, Gliolidin-induced barrier function and macrophage recruitment were altered, larazotide acetate inhibited gliadin-induced macrophage accumulation in the intestine and preserved normal TJ structure[1].
larazotide acetate inhibited transport of gliadin peptides even at 0.1 mM. In animal experiments using BB Wor rats [4] and IL-10 / mice [5], the effective in vivo dose of larazotide acetate is on the order of 0.2-100 μM. Lupus-derived RG strains induced high levels of intestinal permeability that was significantly greater in female than male mice, Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate[9].
References:
[1]: Gopalakrishnan S, Durai M, et,al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides. 2012 May;35(1):86-94. doi: 10.1016/j.peptides.2012.02.015. Epub 2012 Feb 27. PMID: 22401908.
[2]: Gopalakrishnan S, Pandey N, et,al. Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer. Int J Pharm. 2009 Jan 5;365(1-2):121-30. doi: 10.1016/j.ijpharm.2008.08.047. Epub 2008 Sep 11. PMID: 18832018.
[3]: Clemente MG, De Virgiliis S, et,al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003 Feb;52(2):218-23. doi: 10.1136/gut.52.2.218. PMID: 12524403; PMCID: PMC1774976.
[4]: Watts T, Berti I, et,al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. doi: 10.1073/pnas.0500178102. Epub 2005 Feb 14. PMID: 15710870; PMCID: PMC549484.
[5]: Arrieta MC, Bistritz L, et,al. Alterations in intestinal permeability. Gut. 2006 Oct;55(10):1512-20. doi: 10.1136/gut.2005.085373. PMID: 16966705; PMCID: PMC1856434.
[6]: Wang W, Uzzau S, et,al. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000 Dec;113 Pt 24:4435-40. doi: 10.1242/jcs.113.24.4435. PMID: 11082037.
[7]: Gopalakrishnan S, Tripathi A, et,al. Larazotide acetate promotes tight junction assembly in epithelial cells. Peptides. 2012 May;35(1):95-101. doi: 10.1016/j.peptides.2012.02.016. Epub 2012 Feb 28. PMID: 22401910.
[8]: Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384. doi: 10.1080/21688370.2016.1251384. PMID: 28123927; PMCID: PMC5214347.
[9]: Silverman GJ, Deng J,et,al. Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity. Front Immunol. 2022 Aug 11;13:897971. doi: 10.3389/fimmu.2022.897971. PMID: 36032126; PMCID: PMC9405438.
Larazotide acetate（以前称为 AT-001）是一种高度极性的八肽，来源于霍乱弧菌[6]分泌的原核闭合带蛋白。
体外研究表明，醋酸拉拉扎肽可以防止由细胞因子、细菌制剂和麸质片段诱导的紧密连接打开[7,8]。在路西法黄 (LY) 通透性测定中，AT-1002 诱导人源 Caco-2 细胞的 TJ 屏障功能障碍[2]，AT-1002 导致 LY 传代显着增加，这被抑制Larazotide acetate 呈剂量依赖性。 15 和 12.5 mM 的醋酸拉拉扎肽分别显着抑制 AT-1002 诱导的 LY 传代增加 71% 和 38%[1]。 Larazotide acetate抑制麦醇溶蛋白诱导的IEC-6细胞骨架重组[3]。
在麦醇溶蛋白致敏的 HLA-HCD4/DQ8 双转基因小鼠体内，麦醇溶蛋白诱导的屏障功能和巨噬细胞募集发生改变，醋酸拉拉扎肽抑制麦醇溶蛋白诱导的巨噬细胞在肠道中的积累并保持正常的 TJ 结构[1 ].
larazotide acetate 甚至在 0.1 mM 时也能抑制麦醇溶蛋白肽的转运。在使用BB Wor大鼠[4]和IL-10/小鼠[5]的动物实验中，醋酸拉拉扎肽的体内有效剂量为0.2-100微米。狼疮衍生的 RG 菌株诱导高水平的肠道通透性，雌性小鼠明显高于雄性小鼠。令人惊讶的是，口服醋酸拉拉扎肽[9]可完全逆转肠道通透性。
| Cell experiment [1]: | |
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Cell lines |
Caco-2 and IEC6 cells |
|
Preparation Method |
Treatment solutions containing LY with or without AT-1002 and different concentrations of larazotide acetate in HBSS were added to the apical compartment of each monolayer and incubated at 37 °C, 50 rpm for 180 min. |
|
Reaction Conditions |
0-15mM larazotide acetate at 37 °C for 60 min or 180 min, |
|
Applications |
In Lucifer yellow (LY) permeability assays, AT-1002 caused a substantial increase in LY passage, which was inhibited by larazotide acetate in a dose-dependent manner. Larazotide acetate at 15 and 12.5 mM significantly inhibited the AT-1002-induced increase in LY passage by 71 and 38%, respectively. |
| Animal experiment [1]: | |
|
Animal models |
HLA-HCD4/DQ8 mice |
|
Preparation Method |
Mice were gavaged with gliadin (2 mg/mouse), +/ treatment, 2 /week for 7 weeks. Group 1 received larazotide acetate (250 μg/mouse) and gliadin. |
|
Dosage form |
250 μg larazotide acetate /mouse, twice a week for 7 weeks |
|
Applications |
In vivo in gliadin-sensitized HLA-HCD4/DQ8 double transgenic mice, larazotide acetate inhibited gliadin-induced macrophage accumulation in the intestine and preserved normal TJ structure. |
|
References: [1]. Gopalakrishnan S, Durai M, et,al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides. 2012 May;35(1):86-94. doi: 10.1016/j.peptides.2012.02.015. Epub 2012 Feb 27. PMID: 22401908. |
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| Cas No. | 881851-50-9 | SDF | |
| 别名 | 醋酸拉瑞唑来 | ||
| Canonical SMILES | O=C([C@H](C(C)C)NC([C@H](CC(C)C)NC([C@H](C(C)C)NC(CNC(CN)=O)=O)=O)=O)N[C@@H](CCC(N)=O)C(N1[C@@H](CCC1)C(NCC(O)=O)=O)=O.CC(O)=O | ||
| 分子式 | C34H59N9O12 | 分子量 | 785.89 |
| 溶解度 | Water : 16.67 mg/mL (21.21 mM);DMSO : 3.2 mg/mL (4.07 mM) | 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 | 1.2724 mL | 6.3622 mL | 12.7244 mL |
| 5 mM | 0.2545 mL | 1.2724 mL | 2.5449 mL |
| 10 mM | 0.1272 mL | 0.6362 mL | 1.2724 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet