CHEMISTRY/BIOLOGY OF THE GENETICALLY-DISTINCT COLLAGENS

在过去的几年里，该实验室的研究 在确定胶原蛋白分子 共同代表了一个化学性质不同的家族， 功能相关的蛋白质。 一些生物学意义 不同类型的胶原蛋白是强调他们的一般 组织间和组织内的分布模式以及 单个分子种类形成独特和容易的趋势 细胞外空间中可区分的功能聚集体 各种结缔组织。 目前的延续 已制定了一项应用程序，以解决关键的遗留问题 与胶原蛋白家族的分子多样性有关。 的 应用集中在两种定量的“次要”胶原， I.例如，V型和Xi型。该方案的总体目标是 延伸并基本完成了生化特性 这些胶原蛋白及其组成链，并阐明 这些胶原蛋白的化学和拓扑关系， 在选定的组织中更普遍的胶原蛋白。 具体而言是 这些胶原的组织形式将通过从 适当的来源和组成链解决， 色谱技术 在这条被发现的链条中 时尚的特点将在数量和性质方面， CNBr裂解产物，重点是α 3（V）链 和Xi型胶原的1 α链。 利用这些数据， 从以前的研究中获得的信息， V型和Xi型胶原蛋白的模式将作为函数进行评价 与离散肽片段相关的放射性 随后硼氚减少所选组织中的交联。 将对放射性肽进行进一步研究， 辨别由交叉链接连接的链的性质。 在 此外，还对V型和Xi型的能力进行了系统的研究 胶原形成纤维和/或交替的聚集体形式， 单独沉淀和在其它胶原分子存在下沉淀 物种将被淘汰。 最后，收集到的信息 上述研究将得到以下研究的补充： 涉及胶原蛋白的单克隆抗体的制备， 抗体在光和电子定位中的应用 显微镜水平。 预计， 拟议的研究将大大增强当前的信息， 考虑到这些次要胶原蛋白的化学性质， 促进对它们的离散生物学特性进行严格评估， 角色

Investigations in this laboratory over the past several years have been instrumental in establishing that collagen molecules collectively represent a family of chemically-distinct, albeit functionally-related proteins. The biological significance of some of the different types of collagen is underscored by their general distribution pattern among and within tissues as well as the tendency of individual molecular species to form unique and readily distinguishable functional aggregates in the extercellular spaces of various connective tissues. The present continuation application has been formulated to address key remaining issues relevant to the molecular diversity of the collagen family. The application focuses on two of the quantitatively "minor" collagens, i. e., type V and XI. The overall objectives of the program are to extend and essentially complete the biochemical characaterization of these collagens and their constituent chains and elucidate the chemical and topological relationships of these collagens to the more prevalent collagens in selected tissues. Specifically, the tissue forms of these collagens will be prepared by extration from appropriate sources and the constituent chains resolved by chromatographic techniques. Individual chains recovered in this fashion will be characterized with respect to number and nature of the CNBr cleavage products with emphasis on the alpha 3(V) chain and the 1 alpha chain of type XI collagen. Using these data and information available from previous studies, the cross-linking patterns of type V and XI collagen will be evaluated as a function of radioactivity associated with discrete peptide fragments following borotritide reduction of cross-links in selected tissues. Further studies on the radioactive peptides will be conducted to discern the nature of the chains joined by the cross-links. In addition, a systematic study of the ability of type V and XI collagens to form fibrous and/or alternate aggregate forms when precipitated alone and in the presence of other collagen molecular species will be undertaken. And finally, information garnered in the aforementioned studies will be complemented by studies leading to the fabrication of monoclonal antibodies to the collagaens and use of the antibodies for localization at the light and electron microscope levels. It is anticipated that the results of the proposed studies will considerably enhance current information with respect to the chemical properties of these minor collagens and facilitate a critical assessment of their discrete biological roles.