SBIR TOPIC 294 PHASE I - DEVELOPMENT OF GLYCOSYLATION-SPECIFIC RESEARCH REAGENTS

蛋白o - glcnac酰化（n -乙酰氨基葡萄糖修饰）降低磷酸化，在细胞周期调节、细胞凋亡和信号转导中起关键作用。到目前为止，已发现约120个o - glcn酰化的人蛋白。为了阐明o - glcn酰化的功能，有必要开发针对o - glcn酰化蛋白的位点特异性抗体。o - glcn酰化有许多泛特异性抗体。然而，很少有针对o - glcn酰化蛋白的位点特异性抗体被成功地生产出来。

Protein O-GlcNAcylation (N-acetylglucosamine modification), which decreases phosphorylation, plays a critical role in cell-cycle regulation, apoptosis and signal transduction. So far, ~120 O-GlcNAcylated human proteins have been found. To elucidate functions of O-GlcNAcylation, it is necessary to develop site-specific antibodies for O-GlcNAcylated proteins. Many pan-specific antibodies for O-GlcNAcylation are available. However, few site-specific antibodies for O-GlcNAcylated proteins have been successfully produced. During the Phase I study, we will synthesize multiple antigen peptides with various features against O-GlcNAcylation sites of c-myc and p53 to test effects of a specific peptide design on the sensitivity and specificity of the antibodies. Sensitivity and specificity of the antibodies will be determined to find out the best peptide design. We will explore utility of the O-GlcNAcylation site-specific antibodies using human breast cell lines, normal (MCF10A) and tumor cells (MCF-7 and N-ras and H-ras MCF10A) with and without treatment with various O-GlcNAcase inhibitors.