BIOLOGY OF SIALIC ACID SUBSTITUTIONS

唾液酸取代的生物学

• 批准号: 2176545
• 负责人: AJIT P VARKI
• 金额: $ 26.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2176545
• 关键词: acetylation; carbohydrate biosynthesis; carbon; complementary DNA; embryo /fetus; enzyme linked immunosorbent assay; enzyme mechanism; enzyme reconstitution; gangliosides; genetically modified animals; hydrolase; laboratory mouse; laboratory rabbit; laboratory rat; liver metabolism; molecular cloning; monoclonal antibody; neoplastic cell; protein purification; radionuclides; radiotracer; sialate; tissue /cell culture; tritium; western blottings

Many specific biological functions have been attributed to sialic acids. However, most studies of sialic acids do not take into account the diversity generated by modifications of the parent molecule, such as 0-acetylation of the side chain. During the prior funding period, we have developed new and sensitive methods for the analysis of modified sialic acids, identified some new and unexpected molecules, studied sialic acid:O-acetyltransferases from E.Coli., rat liver and human melanoma, identified and characterized sialic acid-specific 0-acetyl-esterases, studied the biosynthesis and turnover of the N-glycolyl group of sialic acids, and discovered a novel de-N-acetylation/re-N-acetylation reaction in melanoma gangliosides. Most recently, we have developed a novel approach to abrogate O-acetylation in the early mouse embryo, and in selected tissues of transgenic mice. In the upcoming grant period, we will focus our attention upon the following: 1. Purification, reconstitution and characterization of the rat liver Sialic Acid O-acetyltransferase(s). 2. Subcellular distribution of O-acetylated sialic acids, and the related enzymes in rat liver. 3. Purification, reconstitution and properties of human melanoma Sialic Acid O-acetyltransferase(s). 4. Mechanisms for de-N-acetylation and re-N-acetylation of sialic acids on gangliosides. 5. Molecular cloning of cDNAs encoding sialic acid specific O-acetyltransferase(s). 6. Abrogation of O-acetylation in the early mouse embryo. 7. Abrogation of O-acetylation in selected tissues of transgenic mice. In the long run, these studies will help us to understand the biological roles of sialic acids and their modifications in health and disease. Our findings to date implicate these molecules in a variety of important roles, including protection from microbial organisms on mucosal surfaces, the modulation of complement activation, the expression of oncofetal antigens in various tumors, and the regulation of cell-cell interaction during the development of certain organs.

许多特定的生物学功能已归因于 唾液酸。 但是，大多数唾液酸的研究都不接受 说明由父分子的修饰产生的多样性， 例如侧链的0-乙酰化。 在先前的资金期间 时期，我们开发了新的和敏感的方法来分析 改良的唾液酸，确定了一些新的和意外的分子， 研究了唾液酸：来自大鼠肝脏和大鼠肝脏和 人类黑色素瘤，被鉴定并表征唾液酸特异性 0-乙酰酯酶研究了生物合成和周转 唾液酸的N-糖基团，发现了一种新颖的 黑色素瘤神经毒素中的DE-N-乙酰化/Re-N-乙酰化反应。 最近，我们开发了一种新颖的方法来消除 早期小鼠胚胎中的o-乙酰化，并在选定的组织中 转基因小鼠。 在即将到来的赠款时期，我们将集中精力 注意以下内容： 1。大鼠肝脏的纯化，重建和表征 唾液酸O-乙酰转移酶（S）。 2。o-乙酰化唾液酸的亚细胞分布，相关 大鼠肝脏中的酶。 3。人黑色素瘤的纯化，重构和特性 酸O-乙酰转移酶（S）。 4。唾液酸的DE-N-乙酰化和重新乙酰化的机制 在神经节苷脂上。 5。编码唾液酸特异性的cDNA的分子克隆 O-乙酰转移酶（S）。 6。在早期小鼠胚胎中废除O-乙酰化。 7。废除转基因小鼠选定组织中的O-乙酰化。 从长远来看，这些研究将帮助我们了解 唾液酸的生物学作用及其在健康中的修饰和 疾病。 迄今为止，我们的发现将这些分子暗示 重要角色，包括保护微生物对粘膜的保护 表面，补体激活的调节，表达 各种肿瘤中的肿瘤抗原和细胞细胞的调节 在某些器官发展过程中的相互作用。