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SALIVARY MUCINS--BIOCHEMICAL AND GENETIC STUDIES

唾液粘蛋白——生物化学和遗传学研究

基本信息

批准号：
2749309
负责人：
MICHAEL J LEVINE
金额：
$ 45.21万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-05-01 至 2000-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2749309
关键词：
glycoprotein structure mucins protein structure function saliva

项目摘要

Our long-range goal is the development of artificial salivas for the treatment of salivary dysfunction. This Program Project Grant (PPG) will study a potentially important ingredient of artificial salivas, namely mucins. The research objectives of the PPG are two-fold. The first is to understand on a molecular level the structure-function relationships of human salivary mucins (higher molecular weight MG1 and lower molecular weight MG2) and how these molecules are made in situ. The second is to enhance these mechanisms through selective endogenous or exogenous molecular manipulation of the host. These goals are being pursued in three integrated projects: (A) Conformation/Bioactivity of Human Salivary Mucin Glycans (Dr. Michael J. Levine, Director); (B) Structure/Regulation of Human Salivary Apo-Mucin Genes (Dr. Libuse A. Bobek, Director); and (C) Regulation of Human Salivary Mucin Glycosylation (DR. Joseph T. Y Lau, Director). Project A will use a biochemical/biophysical approach to synthesize MG2 glycopeptides with varying levels of O-linked units. The bioactivity of these glycopeptides will be compared to native MG2 to assess the role of glycosylation patterns on biological function. In subsequent studies, the data obtained will be used to design mucin peptides (e.g. glycomimetics) that mimic the conformation and biological properties of bioactive glycopeptides. Project B will use a molecular biology approach to study MG2 (MUC7) gene expression and characterize the protein structure of the apo-MG1 monomeric biology approach to examine the molecular and cellular factors that dictate glycan composition in human salivary mucins. Studies will focus on the biosynthesis of the sialylated- and fucosylated-Core 1 oligosaccharides on MG2. Knowledge obtained in all 3 projects could eventually provide a template for the design of bioactive glycomimetics and recombinant mucin analogs for use in artificial salivas and gene therapy protocols for augmenting mucin expression.

我们的长期目标是开发人工唾液，唾液腺功能障碍的治疗。该计划项目补助金（PPG）将研究人工唾液的一种潜在的重要成分，粘蛋白。 PPG的研究目标是双重的。一是在分子水平上理解结构与功能的关系人唾液粘蛋白（高分子量MG 1和低分子量MG 2）的表达重量MG 2）以及这些分子是如何原位制备的。二是通过选择性的内源性或外源性途径增强这些机制对宿主的分子操控这些目标正在努力实现，三个综合项目：（A）人类唾液的构象/生物活性粘蛋白聚糖（Michael J. Levine博士，负责人）;（B）结构/调节人唾液脱辅基粘蛋白基因的研究（Libuse A.博贝克，主任）;以及 (C)人唾液粘蛋白糖基化的调节（Dr. Joseph T. Y 董事）。项目A将使用生物化学/生物物理方法合成MG 2 具有不同水平的O-连接单元的糖肽。的生物活性这些糖肽将与天然MG 2进行比较，以评估糖基化模式对生物学功能的影响。在随后的研究中，所获得的数据将用于设计粘蛋白肽（例如，糖模拟物），其模拟糖的构象和生物学性质。生物活性糖肽。项目B将使用分子生物学方法研究MG 2（MUC 7）基因表达并表征蛋白质 apo-MG 1单体生物学方法的结构，以检查决定人体聚糖组成的分子和细胞因子唾液粘蛋白。研究将集中在生物合成的唾液酸化和岩藻糖基化核心1寡糖对MG 2的影响。在所有3个项目中获得的知识最终可以提供一个模板用于生物活性糖模拟物和重组粘蛋白类似物的设计用于人工唾液和基因治疗方案，粘蛋白表达。