Origins of Substrate Specificity for the ppGalNAcTs

描述（由申请人提供）：粘蛋白型o -链糖基化是一种翻译后修饰，其中蛋白质被碳水化合物链高度修饰。这些寡糖作为细胞间的信息介质，对细胞间的通讯至关重要。粘蛋白o型糖蛋白表达模式的改变被认为与肿瘤细胞的侵袭性和转移性有关。粘蛋白的生物合成是由一组酶启动的，这些酶统称为ppGaINAcTs。描述

DESCRPITION (provided by applicant): Mucin-type O-linked glycosylation is a post-translational modification in which proteins are highly decorated by carbohydrate chains. These oligosaccharides serve as mediators of information between cells and are crucial for cell-cell communication. Changes in expression patterns of mucin-type O-linked glycoproteins is believed to contribute to both the invasive and metastatic properties of tumor cells. The biosynthesis of mucin is initiated by a family of enzymes collectively known as the ppGaINAcTs. Characterization of ppGaINAcT substrate specificity and the properties conferring this specificity for each individual isoform has been a difficult task. We propose to use a unique combination of chemistry and molecular biology to facilitate the further understanding of this enzyme family in a stepwise process. Aim 1. Synthesize and systematically analyze a library of glycopeptides to determine the substrate preference of each ppGaINAcT isoform. Aim 2. Create chimeric enzymes to determine what parts of the protein are responsible for conferring specificity. Finally, Aim 3. To correlate the specificity patterns for various isoforms observed in vitro with substrate preference within cells.