Home>>Peptides>>Larazotide acetate

Larazotide acetate Sale

(Synonyms: 醋酸拉瑞唑来) 目录号 : GC33822

醋酸拉唑肽是一种合成肽。

Larazotide acetate Chemical Structure

Cas No.:881851-50-9

规格 价格 库存 购买数量
1mg
¥625.00
现货
5mg
¥1,339.00
现货
10mM (in 1mL Water)
¥1,852.00
现货
25mg
¥4,641.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment [1]:

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 [2]:

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.

产品描述

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。

Chemical Properties

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。
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。

溶解性数据

制备储备液
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
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

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
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

Research Update

Larazotide acetate: a pharmacological peptide approach to tight junction regulation

Am J Physiol Gastrointest Liver Physiol 2021 Jun 1;320(6):G983-G989.PMID:33881350DOI:10.1152/ajpgi.00386.2020.

Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function. LA is currently being studied in phase III clinical trials and is orally administered to adult patients with celiac disease as an adjunct therapeutic to enhance intestinal barrier function that has been disrupted by gliadin-induced immune reactivity. Mechanistically, LA is thought to act as a zonulin antagonist to reduce zonulin-induced increases in barrier permeability and has been associated with the redistribution and rearrangement of tight junction proteins and actin filaments to restore intestinal barrier function. More recently, LA has been linked to inhibition of myosin light chain kinase, which likely reduces tension on actin filaments, thereby facilitating tight junction closure. Small (rodent) and large (porcine) animal studies have been conducted that demonstrate the importance of LA as a tight junction regulatory peptide in conditions other than celiac disease, including collagen-induced arthritis in mice and intestinal ischemic injury in pigs.

Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials

Clin Res Hepatol Gastroenterol 2022 Jan;46(1):101782.PMID:34339872DOI:10.1016/j.clinre.2021.101782.

Purpose: The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD. Methods: We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model. Results: Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4-2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups. Conclusions: AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.

Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions

PLoS One 2021 Apr 22;16(4):e0250165.PMID:33886649DOI:10.1371/journal.pone.0250165.

Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-dependently hasten recovery of intestinal ischemic injury via modulation of TJs. Ischemia-injured tissue from 6-8-week-old pigs was recovered in Ussing chambers for 240-minutes in the presence of LA. LA (1 μM but not 0.1 μM or 10 μM) significantly enhanced transepithelial electrical resistance (TER) above ischemic injured controls and significantly reduced serosal-to-mucosal flux LPS (P<0.05). LA (1 μM) enhanced localization of the sealing tight junction protein claudin-4 in repairing epithelium. To assess for the possibility of fragmentation of LA, an in vitro enzyme degradation assay using the brush border enzyme aminopeptidase M, revealed generation of peptide fragments. Western blot analysis of total protein isolated from uninjured and ischemia-injured porcine intestine showed aminopeptidase M enzyme presence in both tissue types, and mass spectrometry analysis of samples collected during ex vivo analysis confirmed formation of LA fragments. Treatment of tissues with LA fragments had no effect alone, but treatment with a fragment missing both amino-terminus glycines inhibited barrier recovery stimulated by 1 μM LA. To reduce potential LA inhibition by fragments, a D-amino acid analog of larazotide Analog #6, resulted in a significant recovery response at a 10-fold lower dose (0.1 μM) similar in magnitude to that of 1 μM LA. We conclude that LA stimulates repair of ischemic-injured epithelium at the level of the tight junctions, at an optimal dose of 1 μM LA. Higher doses were less effective because of inhibition by LA fragments, which could be subverted by chirally-modifying the molecule, or microdosing LA.

Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis

Nat Commun 2020 Apr 24;11(1):1995.PMID:32332732DOI:10.1038/s41467-020-15831-7.

Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist Larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.

Larazotide acetate promotes tight junction assembly in epithelial cells

Peptides 2012 May;35(1):95-101.PMID:22401910DOI:10.1016/j.peptides.2012.02.016.

Tight junctions (TJ) control paracellular permeability and apical-basolateral polarity of epithelial cells. Dysregulated permeability is associated with pathological conditions, such as celiac disease and inflammatory bowel disease. TJ formation is dependent on E-cadherin-mediated cell-cell adhesion and actin rearrangement, and is regulated by the Rho family GTPase and aPKC signaling pathways. Larazotide acetate, an 8-mer peptide and TJ modulator, inhibits TJ disassembly and dysfunction caused by endogenous and exogenous stimuli in intestinal epithelial cells. Here, we examined the effect of Larazotide acetate on de novo TJ assembly using 2 different model systems. In MDCK cells, Larazotide acetate promoted TJ assembly in a calcium switch assay. Larazotide acetate also promoted actin rearrangement, and junctional distribution of zonula occludens-1 (ZO-1), occludin, claudins, and E-cadherin. Larazotide acetate promoted TJ maturation and decreased paracellular permeability in "leaky" Caco-2 cells. Taken together, our data indicate that Larazotide acetate enhances TJ assembly and barrier function by promoting actin rearrangement and redistribution of TJ and AJ proteins.