Development of Site-specific Arg-GlcNAc Antibodies

位点特异性 Arg-GlcNAc 抗体的开发

• 批准号: 9925239
• 负责人: Marla Popov
• 金额: $ 14.85万
• 依托单位: GLYCOSCIENTIFIC, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-02 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925239
• 关键词: Affinity; Animal Model; Antibiotic Resistance; Antibiotics; Antibodies; Arginine; Bacteria; Biochemistry; Biological Assay; Cell physiology; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Citrobacter rodentium; Communities; Death Domain; Development; Diarrhea; Economics; Enzymes; Equipment; Escherichia coli; Escherichia coli EHEC; FADD protein; Family; Future; Generations; Glucosamine; Glyceraldehyde-3-Phosphate Dehydrogenases; Gram-Negative Bacteria; Hemolytic-Uremic Syndrome; Hospitalization; Human; Immune response; Immune system; Immunization; Immunoprecipitation; In Vitro; Infection; Injections; Mammals; Measures; Medical; Methodology; Microbiology; Modification; Monitor; Monoclonal Antibodies; Mus; Names; Organism; Pathogenesis; Pathogenicity; Pharmacy (field); Phase; Play; Procedures; Process; Protein-Carbohydrate Interaction; Proteins; Public Health; Research; Research Personnel; Resistance; Role; Salmonella; Salmonella enterica; Sampling; Site; Specificity; Structure; TRADD gene; Tertiary Protein Structure; Tumor Necrosis Factor Receptor; UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; Virulence; Wages; Western Blotting; combat; cost; fighting; foodborne; foodborne illness; foodborne outbreak; glycosyltransferase; guanidinium; in vivo; inflammatory disease of the intestine; inhibitor/antagonist; mortality; novel; pathogen; pathogenic Escherichia coli; recombinant peptide; sugar; treatment strategy

Human pathogenic gram-negative bacteria, such as Escherichia coli (E. Coli) and Salmonella enterica cause millions of deaths, thousands of fatalities and billions of dollars in medical expenses and lost wages. A critical process that enables these organisms to overcome the hosts immune response is the injection of proteins directly into infected mammalian (host) cells. Some of these injected effectors, function as enzymes that modify the structure/function of the host proteins, which in turn diminish the cells' ability to fight off the infection. One family of these enzymes are N-glycosyltransferases, which appear to play critical, but yet unknown, function in pathogenicity. These enzymes add a single α-N-acetyl-D-glucosamine (GlcNAc) to the guanidinium groups of arginine residues. The primary focus of this application is to evaluate/develop methodology that will enable the generation of site-specific α-N-GlcNAc antibodies. We feel that this ability will open the door to the creation of a wide range of Abs that will have a wide-ranging impact the fields of pharmacy, microbiology, and biochemistry.

人类致病性革兰氏阴性菌，如大肠杆菌（E.大肠杆菌）和 肠道沙门氏菌导致数百万人死亡，数千人死亡和数十亿美元的损失。 医疗费和工资损失。一个关键的过程使这些生物能够克服 宿主的免疫反应是将蛋白质直接注射到受感染的哺乳动物（宿主）中， 细胞这些注射的效应物中的一些作为酶起作用，所述酶修饰细胞的结构/功能。 宿主蛋白质，这反过来又降低了细胞抵抗感染的能力。One系列 这些酶是N-糖基转移酶，它们似乎起关键作用，但还不为人所知， 在致病性中的作用。这些酶将单个α-N-乙酰基-D-葡糖胺（GlcNAc）添加到 精氨酸残基的胍基。此应用程序的主要重点是 评价/开发能够生成位点特异性α-N-GlcNAc的方法 抗体的我们认为，这种能力将打开大门，创造一个广泛的抗体， 将对药学、微生物学和生物化学领域产生广泛的影响。