Characterization of the Digitalis Receptor and Digitalis Mimics

洋地黄受体和洋地黄模拟物的表征

• 批准号: 9422022
• 负责人: William Ball
• 金额: $ 3.5万
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-15 至 1996-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9422022&HistoricalAwards=false
• 关键词: Characterization; Digitalis; Receptor; Mimics

; R o o t E n t r y F ! Lr C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l mÕGr mÕGr 2 3 4 5 6 7 8 9 : ; F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; E +E @t E u ~ u E +E = u t F E U F V t E U v n E U - F V v RP X # t0 E + Hu& 9E u 9U u W u u O$ ^_ v ~ F V ~ ~ t e tq t& ~ '@;E ~# } u E @;E | } } 9422022 Ball The long term goal of this research is to gain an understanding of the structure and functioning of the cation transporter, Na,K ATPase, with a particular interest in elucidating the molecular mechanisms of digitalis (cardiac glycosides) binding and inhibition of this enzyme. The P.I. proposes to use a relatively new and perhaps unconventional approach to identify and characterize short peptide sequences which may mimic the glycosides, which are nonpeptidic steroid based plant products. The peptides will be selected from bacteriophage contained "random peptide libraries". The diversity of these selected peptides will help us understand how the glycosides bind and how their actions may be modified. In addition, since the enzyme's digitalis binding site has not been determined, the P.I. will also attempt to use anti idiotypic antibodies (raised to anti digoxin antibodies) to identify the binding site. The random peptide libraries will also be used to determine whether it is possible to generate a model digitalis binding site(s) This work has the potential of enabling us to identify serum proteins which serve as natural regulatory proteins. %%% The Na,K-ATPase is a membrane bound enzyme that uses energy in the form of ATP to transport sodium and potassium ions across the cell membrane. It is this maintenance of the levels of these two important cations that is the driving force for the active transport of small molecules such as amino acids, glucose, phosphate and calcium, as well as providing the basis for the action potential in nerve and muscle cells. The Na, K-ATPase is also the receptor for digitalis, a plant glycoside, which inhibits the enzyme in a highly specific manner. This project uses a new immunological approach to learn more about the mechanism of digitalis binding, and should in addition help in identifying the long sought after natural, or endogenous, molecule that acts to regulate the enzyme. ....()()))()() ; Oh +' 0 $ H l D h R:\WWUSER\TEMPLATE\NORMAL.DOT marcia steinberg marcia steinberg @ ? n @ @ (r S u m m a r y I n f o r m a t i o n ( 1 @ NZ Microsoft Word 6.0 2 e 3 e " " " " " " " L L L L L d n L C x | | | | | | | _ P T 4 " | | | | | | " " | x | | | | " | " | 6 " " " " | | 3 | 9422022 Ball The long term goal of this research is to gain an understanding of the structure and functioning of the cation transporter, Na,K ATPase, with a particular interest in elucidating the molecular mechanisms of digitalis (cardiac glycosides) binding and inhibition of this enzyme. The P.I. proposes to use a relatively new and perhaps unconventional approach to identify and characterize short peptide sequences which may mimic the glycosides, which are nonpeptidic steroid based plant products. The peptides will be selected from bacteriophage contained "random p

; 根条目 F ! Lr 组合对象 Word 对象池 mÕGr mÕGr 2 3 4 5 6 7 8 9 : ; F Microsoft Word 6.0 文档 MSWordDoc Word.Document.6 ; u ~ u E +E = u t F E U F V t E U v n EU - F V v RP Ball 这项研究的长期目标是了解阳离子转运蛋白 Na,K ATP 酶的结构和功能， P.I. 对阐明洋地黄（强心苷）结合和抑制这种酶的分子机制特别感兴趣，建议使用一种相对较新且可能非常规的方法来识别和表征可能模仿非肽类固醇的短肽序列。这些肽将从包含“随机肽库”的噬菌体中选择，这些选定肽的多样性将帮助我们了解糖苷如何结合和结合。此外，由于尚未确定酶的洋地黄结合位点，P.I. 还将尝试使用抗独特型抗体（抗地高辛抗体）来识别随机肽库。用于确定是否可以生成模型洋地黄结合位点 这项工作有可能使我们能够识别充当天然调节蛋白的血清蛋白 %%% Na,K-ATP 酶是膜结合的。酶那使用 ATP 形式的能量将钠离子和钾离子穿过细胞膜，这两种重要阳离子的水平的维持是小分子（例如氨基酸、葡萄糖、磷酸盐）主动运输的驱动力。 Na、K-ATP 酶也是洋地黄（一种植物糖苷）的受体，它以高度特异性的方式抑制该酶。新的免疫学方法了解更多关于洋地黄结合的机制，并且还应该有助于识别长期寻求的天然或内源性分子，其作用是调节酶....()()))()() Oh +' 0 ; $ H l D h R:\WWUSER\TEMPLATE\NORMAL.DOT marcia steinberg marcia steinberg @ ? n @ @ (r 摘要信息 ( 1 @ NZ微软Word 6.0 e ” ” ” ” L L L L d n L C x | | | | | _ P T 4 ” | | ” | ” | " " " | | 3 | 9422022 Ball 这项研究的长期目标是了解阳离子转运蛋白 Na,K ATP 酶的结构和功能，特别感兴趣的是阐明了洋地黄（强心苷）结合和抑制这种酶的分子机制，P.I.建议使用一种相对较新且可能非常规的方法来识别和表征可能模拟苷的短肽序列，而苷是基于非肽类固醇的植物产品。肽将从包含“随机p”的噬菌体中选择