CHEMISTRY/BIOLOGY OF THE GENETICALLY-DISTINCT COLLAGENS

在过去的几年里，这个实验室的调查结果 在建立胶原分子方面发挥了重要作用 共同代表了一个化学上截然不同的家族，尽管 与功能相关的蛋白质。某些基因的生物学意义 不同类型的胶原蛋白的区别在于它们的一般 组织间和组织内的分布格局以及 个别分子物种形成独特且容易形成的趋势 胞外空间中可区分的功能聚集体 各种结缔组织。现在的延续 已制定申请，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。这个 应用主要集中在两种定量的“次要”胶原蛋白上， 即V型和XI型。该计划的总体目标是 延伸并基本完成生化表征 这些胶原蛋白和它们的组成链，并阐明 这些胶原蛋白与血管内皮细胞的化学和拓扑关系 在选定的组织中更普遍的胶原蛋白。具体地说， 这些胶原蛋白的组织形式将通过从 适当的来源和组成链由 层析技术。在这个过程中找到了单独的链条 时尚将以数量和性质为特征 强调α3(V)链的CNBr裂解产物 XI型胶原蛋白的1α链。使用这些数据和 从以前的研究中获得的信息，交叉链接 V型和XI型胶原的模式将作为一种功能进行评估 与离散的多肽片段相关的放射性 在选定组织中的交联链的硼三肽还原之后。 将对放射性多肽进行进一步研究，以 辨别由交叉链连接的链条的性质。在……里面 此外，对V型和XI型能力的系统研究 胶原蛋白在以下情况下形成纤维状和/或交替聚集形式 单独和在其他胶原分子存在的情况下沉淀 将承担物种保护的任务。最后，收集到的信息 上述研究将得到以下研究的补充 制备抗胶原和抗胶原蛋白的单抗 利用抗体对光和电子进行定位 显微镜水平。预计此次评选的结果 拟议的研究将大大增强当前的信息， 尊重这些次要胶原蛋白的化学性质 促进对其离散生物的批判性评估 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.