Enzymatic Degradation of Glycosaminoglycans

描述(申请人提供)：糖胺多聚糖(GAG)是一种复杂的多糖，在真核细胞的细胞-细胞外基质(ECM)界面上大量存在。在理解细胞-细胞外基质相互作用的动态性质(历史上，细胞外基质被认为是一种使细胞水化的惰性物质)在影响细胞和更高级别组织和器官水平的表型方面的重要性方面，已经发生了范式转变。这一范例的核心是化学上不同种类的GAG与细胞外环境中的众多蛋白质之间的特定相互作用。因此，了解GAG的结构-功能关系作为一个基础领域以及它在识别新的治疗靶点方面的潜力都变得重要起来。然而，过去实现这一目标的进展有限，因为GAG的多分散性和化学异质性给其分离和表征带来了许多挑战。几年来，我们一直致力于解决这些挑战，开发可预测的GAG解聚工具来解码其序列信息，并开发敏感的分析技术来准确检测和表征细胞或组织中极少量的GAG。重点关注两类重要的恶作剧，即。HSGAGs和CSGAGs我们已经成功地展示了我们的工具在开发快速和强大的GAG测序技术方面的效用。在这项研究中，我们试图扩展我们的工具的开发，专注于HSGAG和CSGAG结构-功能关系的生化和生物学方面。最后，我们寻求开发一个数据库平台来捕获和传播与GAG结构功能关系有关的信息和数据，这是在GAG研究领域中的一种新方法。我们相信，我们的研究将真正加快理解基础生物过程中的Gag-结构-功能关系的进展-这一研究领域正变得越来越重要。

DESCRIPTION (provided by applicant): Glycosaminoglycans (GAGs) are complex polysaccharides found in abundance at the cell-extracellular matrix (ECM) interface of eukaryotic cells. There has been a paradigm shift in understanding the importance of the dynamic nature of the cell-ECM interactions (historically the ECM was considered an inert material that hydrated the cells) in influencing phenotype at cellular and higher order tissue and organ levels. At the heart of this paradigm are the specific interactions between the chemically heterogeneous GAGs and numerous proteins in the extracellular environment. Thus, understanding the structure-function relationship of GAGs has gained importance both as a fundamental field and for its potential in identification of novel therapeutic targets. However, progress towards this goal has been limited in the past due to the polydispersity and chemical heterogeneity of GAGs that posed numerous challenges for their isolation and characterization. For several years, we have focused our efforts in addressing these challenges to develop enzymatic tools for predictable depolymerization of GAGs to decode their sequence information as well as sensitive analytical techniques to accurately detect and characterize extremely small amounts of GAGs available from cells or tissues. Focusing on the 2 important classes of GAGs viz. HSGAGs and CSGAGs we have successfully demonstrated the utility of our tools to develop rapid and robust technologies for sequencing GAGs. In this study we seek to expand on the development of our tools to focus on biochemical and biological aspects of HSGAG and CSGAG structure-function relationships. Finally, we seek to develop a database platform to capture and disseminate information and data pertaining to GAG structure function relationships which is a novel approach in the context of the GAG research area. We believe that our study would truly accelerate the progress of understanding GAG-structure-function relationships in fundamental biological processes-a research area that is gaining increasing importance.