PROTAMINE HYPERSENSITIVITY AND POLYION BIOLOGY

鱼精蛋白过敏和多离子生物学

• 批准号: 3133321
• 负责人: John M Weiler
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3133321
• 关键词: affinity chromatography; anticoagulants; chemical structure function; complement; complement inhibitors; complement pathway; delayed hypersensitivity; drug adverse effect; drug design /synthesis /production; drug hypersensitivity; eosinophil; gel electrophoresis; heart surgery; heparin; high performance liquid chromatography; human subject; immediate hypersensitivity; immunoglobulin E; immunoglobulin G; immunotoxicity; polysaccharides; protamines; protein sequence

Protamine sulfate, a strong polycation, is used extensively in clinical medicine to block anticoagulant activity to heparin, a strong polyanion. Recent studies indicate that protamine may be a major cause of morbidity and mortality in patients who undergo cardiopulmonary bypass and that these reactions are not predictable in most cases. Furthermore, new low molecular weight heparins may not be as easy to neutralize as commercial heparin. Therefore, a new agent is urgently needed, to replace protamine, to block the anticoagulant activity of heparin without itself having anticoagulant or procoagulant activity or capacity to cause Type I hypersensitivity or to act on complement. One major mechanism by which polyions exert activity in vivo appears to be through the complement system. These studies will investigate a variety of polyions for capacity to regulate complement using state-of- the-art assays (Section D.2). Polyanions (polydisperse heparin and monodisperse heparin oligosaccharides) will be examined in detail to determine the structure and activity relationship for activity on complement (Section D.3). Polycations will be studied to determine specific mechanisms by which these basic substances regulate complement and again to determine the structure and activity relationship (Section D.4). The mechanism by which polycations preferentially inhibit the classical and polyanions preferentially inhibit the alternative pathways of complement will be determined (Section D.5). Affinity chromatography will be combined with conventional chromatography to purify heparin oligosaccharides with high capacity to bind complement (Section D.6). These heparin oligosaccharides will be studies for binding affinity to protamine, complement and a variety of polycations (Section D.7). These investigations will also determine the sequences in Hep which have high affinity for C3 and the sequence in C3 to which Hep binds. These studies should provide a more complete understanding of the complex role that polyions play in regulating complement activity and could lead to the development of new pharmacological agents.

硫酸鱼精蛋白是一种强多阳离子，广泛应用于临床

项目成果

Regulation of C5 convertase activity by properdin, factors B and H.

备解素、因子 B 和 H 调节 C5 转化酶活性。

• DOI: 10.1007/bf02935515
• 发表时间: 1989
• 期刊: Immunologic research
• 影响因子: 4.4
• 作者: Weiler,JM

Heparin and modified heparin inhibit complement activation in vivo.

• DOI: 10.4049/jimmunol.148.10.3210
• 发表时间: 1992-05
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: J. Weiler;R. E. Edens;R. J. Linhardt;D. Kapelanski

Eosinophil granule cationic proteins regulate complement. I. Activity on the alternative pathway.

嗜酸性粒细胞颗粒阳离子蛋白调节补体。

• 发表时间: 1992
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Weiler,JM;Edens,RE;Gleich,GJ
• 通讯作者: Gleich,GJ

Eosinophil granule major basic protein regulates generation of classical and alternative-amplification pathway C3 convertases in vitro.

嗜酸性粒细胞颗粒主要碱性蛋白在体外调节经典和替代放大途径 C3 转化酶的产生。

• 发表时间: 1988
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Weiler,JM;Gleich,GJ
• 通讯作者: Gleich,GJ

Structure and activity of a unique heparin-derived hexasaccharide.

独特的肝素衍生六糖的结构和活性。

• 发表时间: 1986
• 期刊: The Journal of biological chemistry
• 作者: Linhardt,RJ;Rice,KG;Merchant,ZM;Kim,YS;Lohse,DL
• 通讯作者: Lohse,DL