Development of Site-specific Arg-GlcNAc Antibodies

人类致病性革兰氏阴性细菌，如大肠杆菌(E.Coli)和 肠道沙门氏菌导致数百万人死亡，数千人死亡，数十亿美元 医疗费用和工资损失。一个关键的过程，使这些有机体能够克服 宿主的免疫反应是将蛋白质直接注入受感染的哺乳动物(宿主)。 细胞。这些注射的效应器中的一些作为酶发挥作用，改变 宿主蛋白，这反过来又降低了细胞抵御感染的能力。一个家庭 这些酶是N-糖基转移酶，它们似乎发挥着关键的作用，但尚不清楚， 在致病性中起作用。这些酶将单一的α-N-乙酰-D-氨基葡萄糖(GlcNAc)添加到 精氨酸残基中的胍基。此应用程序的主要关注点是 评估/制定能够生成特定部位α-N-GlcNAc的方法 抗体。我们认为，这种能力将打开创造广泛的抗体的大门， 将在制药、微生物学和生物化学领域产生广泛的影响。

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.