Larazotide acetate |
| Catalog No.GC33822 |
라라조티드 아세테이트(구 AT-001)는 진균성 조물결 밀착 단백질에서 유래된 고극성 옥타펩타이드로, 비브리오 콜레라에 의해 분비됩니다.
Products are for research use only. Not for human use. We do not sell to patients.
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.
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