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乳糜泻联合酶疗法的合理设计

Rational design of combination enzyme therapy for celiac sprue.

作者信息

Siegel Matthew, Bethune Michael T, Gass Jonathan, Ehren Jennifer, Xia Jiang, Johannsen Alexandre, Stuge Tor B, Gray Gary M, Lee Peter P, Khosla Chaitan

机构信息

Department of Chemical Engineering, Stanford University, Stanford, California 94305, USA.

出版信息

Chem Biol. 2006 Jun;13(6):649-58. doi: 10.1016/j.chembiol.2006.04.009.

DOI:10.1016/j.chembiol.2006.04.009
PMID:16793522
Abstract

Celiac sprue (also known as celiac disease) is an inheritable, gluten-induced enteropathy of the upper small intestine with an estimated prevalence of 0.5%-1% in most parts of the world. The ubiquitous nature of food gluten, coupled with inadequate labeling regulations in most countries, constantly poses a threat of disease exacerbation and relapse for patients. Here, we demonstrate that a two-enzyme cocktail comprised of a glutamine-specific cysteine protease (EP-B2) that functions under gastric conditions and a PEP, which acts in concert with pancreatic proteases under duodenal conditions, is a particularly potent candidate for celiac sprue therapy. At a gluten:EP-B2:PEP weight ratio of 75:3:1, grocery store gluten is fully detoxified within 10 min of simulated duodenal conditions, as judged by chromatographic analysis, biopsy-derived T cell proliferation assays, and a commercial antigluten antibody test.

摘要

乳糜泻(也称为腹腔疾病)是一种遗传性的、由麸质引起的上小肠肠病,在世界大部分地区估计患病率为0.5%-1%。食物中麸质的普遍存在,再加上大多数国家标签法规不完善,不断对患者构成疾病加重和复发的威胁。在此,我们证明,一种由在胃部条件下起作用的谷氨酰胺特异性半胱氨酸蛋白酶(EP-B2)和在十二指肠条件下与胰腺蛋白酶协同作用的肽酶组成的双酶混合物,是乳糜泻治疗的一个特别有效的候选物。通过色谱分析、活检来源的T细胞增殖试验和商业抗麸质抗体检测判断,在麸质:EP-B2:肽酶重量比为75:3:1时,杂货店麸质在模拟十二指肠条件下10分钟内可完全解毒。

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