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Domain Structure Elucidation Of Decorin Glycosaminoglycans And The Primary Research For Its Anticancer Activity

Posted on:2016-06-18Degree:MasterType:Thesis
Country:ChinaCandidate:C L WuFull Text:PDF
GTID:2284330464952093Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
Decorin is composed of one glycosaminoglycan(GAG) c hain covalently attached to a protein core, it is an important component of extracellular matrix, its interactions with matrix and cell membrane components have been implicated in many physiological and pathophysiological processes especially in the process of the occurrence and development of tumor. In recent years, there are more and more clinical researches about Decorin, it has recently emerged as a potential natural anticancer agent produced by normal host cells against cancer cells. As the increasing attention of Decorin as well as the progress of modern research technology, the study of the structure of Decorin had further development. For a long time, most of the study focused on the core protein of Decorin, its sequence analysis and spatial structure is relatively clear, GAG chain structure are still not entirely clear, although it has made certain progress, mainly due to its structure complexity and tissue specificity. We still need to do more research on Decorin GAG chain.This research aims at glycosaminoglycan chain, we put forward the following problems: 1.what is the detailed structure of Decorin GAG chain?2. Whether different organizations sources of Decorin have different GAG chain structure?3. Whether Decorin with different glycosaminoglycan chain structures will express different biological activities? To address above questions, several work have been done. First of all, this study established a set of efficient preparation processes, by which a certain amount of Decorin samples were prepared from porcine cartilage and porcine skin tissue, respectively. It is a very solid foundation for the subsequent research of Decorin. Then we analyzed and compared the structure of Decorin GAG chains from different sources through disaccharides, oligosaccharides analysis. In this work, we investigated four types of HILIC resins for optimal HPLC-MS analysis of GAG oligosaccharides having different charge densities. The developed method was successfully applied in the analysis of Decorin GAG oligosaccharides. The result showed that GAG chains from two Decorins have obvious differences in CS/DS composition and sulfation distribution. Finally this study set, antitumor activity of two Decorins was investigated on a lung cancer cell line(H1299) as research model from proliferation and. The results showed that two Decorins with different GAG chains have different proliferatio n and motion aspects.
Keywords/Search Tags:Decorin, structure, sequence, glycosaminoglycan antitumor
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