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VON WILLEBRAND FACTOR--CHEMICAL CHARACTERIZATION

血管性血友病因子--化学特性

基本信息

批准号：
3340720
负责人：
KOITI TITANI
金额：
$ 19.59万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-01-01 至 1986-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3340720
关键词：
chemical cleavage chemical structure function chromatography coagulation factor VIII disulfide bond electrophoresis human tissue ligands pathologic process platelets proteolysis von Willebrand's disease

项目摘要

This is a proposal to undertake a study of the structural features of human von Willebrand Factor, an unusually large oligomeric glycoprotein (subunit size ca 200,000 daltons) which play an important role in hemostasis and blood coagulation. Particular emphasis will be given to elucidation of its complete primary structure and to correlation of defined substructuraldomains with its capability to bind platelets or lolagen. Appropriate attention will be given to the identification of sites of co- or post-translational modification, including glycosylation and disulfide bridging. The protein will be purified in gram quantities from a commercial Factor VIII concentrate and the number and identity to constituent polypeptide chains will be established by chemical means. The whole protein, before or after disulfide reduction, will be fragmented by limited proteolysis to provide substructural domains which will be tested for residual or modified biological function. The whole denatured protein will aslo be cleaved at asparaginyl-glycine, aspartyl-proline, methionyl or arginyl bonds to generate large fragments. The products of the various cleavage reaction will be purified and subjected to sequence analysis. Integration of these results is expected to provide the complete amino acid sequence. Met, Trp and Cys containing peptides will be selectively isolated and analyzed for their design potential for synthetic oligonucleotide hybridization probes. A long-term goal of this study is to seek the chemical basis of dysfunction in the bleeding disorders termed von Willebrand's disease. The proposed structural analysis should provide a chemical framework within which questions of supramolecular organization and dysfunction can be answered in specific terms.

这是一项对人类结构特征进行研究的建议