NONINFLAMMATORY GLUTEN PEPTIDE ANALOGUES AS BIOMARKERS FOR CELIAC SPRUE

非炎症性麸质肽类似物作为乳糜泻的生物标志物

• 批准号: 8172996
• 负责人: KAROL SESTAK
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172996
• 关键词: Animals; Biological Markers; Celiac Disease; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Drug Metabolic Detoxication; Enterocytes; Funding; Glutamine; Gluten; Grant; Immune System Diseases; In Vitro; Inflammatory; Institution; Intestines; Patients; Peptide Hydrolases; Peptides; Permeability; Pharmaceutical Preparations; Research; Research Personnel; Resistance; Resources; Small Intestines; Source; Stomach; T-Lymphocyte; Transglutaminases; United States National Institutes of Health; gastrointestinal; peptide analog; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for non-invasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized non-inflammatory gluten peptide analogues in which key Gln residues are replaced by Asn or His. Like their pro-inflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2 or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 需要新的工具来管理小肠的终生免疫疾病腹腔泉水。 正在进行的药物试验还促使人们寻找麸质诱导的肠道变化的非侵入性生物标志物。 我们已经合成并表征了非炎性麸质肽类似物，其中关键的GLN残基被ASN或HEN取代。 像促炎的同类产品一样，这些生物标志物对胃肠道蛋白酶具有抵抗力，容易受到麸质酶的影响，并且可以在肠肠层中渗透。 然而，与麸质肽不同，它们并不能被转谷氨酰胺酶，HLA-DQ2或疾病特异性T细胞明显地识别。 体外和动物研究表明，生物标志物可以检测到肠道通透性的变化以及麸质酶催化的胃解毒。 因此，有必要对受控的临床研究评估这些肽作为腹腔患者中肠道通透性异常的探针和临床试验和实践中的麸质酶功效。