PROTEOGLYCAN STRUCTURE, FUNCTION AND METABOLISM

蛋白聚糖是结缔组织中普遍存在的成分。 他们经常 作为这些组织的细胞外基质的主要成分出现。 软骨蛋白聚糖已得到最彻底的研究，并且它们已经 作为检测蛋白聚糖结构和功能的有用模型 在其他更复杂的结缔组织基质中。 仔细的分析 蛋白聚糖结构的常规生物化学方法已经被 复杂的内在异质性和多元性的 蛋白聚糖本身。 免疫学方法提供了 产生特异性识别不同抗原的抗体 存在于蛋白聚糖和连接蛋白上的决定簇。 近期 单克隆抗体程序的引入提供了 产生抗体，这些抗体特异性地识别结构和 生物大分子上的功能性抗原决定簇。 在这 我们计划生产和表征单克隆抗体， 识别蛋白聚糖和连接蛋白上的特定决定簇。 的 抗体的特异性将使用生物化学方法测定， 和免疫测定程序中。 特异性抗体将用于 组织的定量、鉴定、纯化和测定问题 蛋白多糖和连接蛋白的分布。 免疫化学研究 分离的材料和免疫组织化学程序将被采用。 这项提案的一个主要目标是使用特异性单克隆抗体 作为表征和纯化连接的肽片段的手段， 蛋白质和蛋白聚糖。 这些肽将用于测定 连接蛋白的氨基酸序列（一级结构）， l蛋白聚糖 此外，识别免疫球蛋白的功能方面的抗体也可以用于免疫球蛋白。 蛋白聚糖和连接蛋白的相互作用将用于研究 确定蛋白聚糖的结构功能关系 聚集体形成 一个较长期的目标是将这些研究扩展到 更好地了解蛋白多糖代谢， 复杂的结缔组织 这些研究将增加我们对 结缔组织在正常情况下和疾病中的功能。

Proteoglycans are ubiquitous components of connective tissues. They often occur as major components of the extra-cellular matrix of these tissues. Cartilage proteoglycans have been the most thoroughly studied and they have served as a useful model for examining proteoglycan structure and function in other more complex connective tissue matrices. Detailed analysis of proteoglycan structure by conventional biochemical procedures has been complicated by the inherent heterogeneity and polydisperisty of the proteoglycans themselves. Immunological methods offer the possibililty of raising antibodies which specifically recognize different antigenic determinants present on proteoglycans and link protein. The recent introduction of monoclonal antibody procedures has offered the possiblity of producing antibodies which specifically recognize structural and functional antigenic determinants on biological macromolecules. In this proposal we plan to produce and characterize monoclonl antibodies that recognize specific determinants on proteoglycan and link protein. The specificity of the antibodies will be determined using biochemical methods, and in immunoassay procedures. Specific antibodies will be applied to problems of quantitating, identifying, purifying and determining the tissue distribution of proteoglycan and link protein. Both immunochemical studies on isolated material and immunohistochemical procedures will be employed. A major objective of this proposal is to use specific monoclonal antibodies as a means of characterizing and purifying peptide fragments of link protein and proteoglycan. These peptides will be used in the determination of the amino acid sequences (primary structure) of link protein and lproteoglycan. In addition, antibodies recognizing functional aspects of proteoglycan and link protein interactions will be used instudies determining structure function relationships involved in proteoglycan aggregate formation. A longer term objective is to extend these studies to gain a better understanding of proteoglycan metabolism in other more complex connective tissues. These studies will increase our knowledge of connective tissue function in normal conditions and in disease.