Synthesis of Ion Channel Forming Peptides

离子通道形成肽的合成

• 批准号: 9708649
• 负责人: Karin Akerfeldt
• 金额: $ 22.5万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 1998-12-04
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9708649&HistoricalAwards=false
• 关键词: Synthesis; Ion; Channel; Forming; Peptides

With the support of a Research in Undergraduate Institutions award from the Organic Synthesis Program and the Office of Multidisciplinary Activities of the Mathematical and Physical Sciences Directorate, Professor Karin S. Akerfeldt, of the Department of Chemistry at Rutgers, the State University of New Jersey, Camden Campus, carries out the synthesis and analysis of ion channel forming peptides. Structurally well-defined artificial proton selective channels are synthesized as models to study the fundamental mechanisms involved in proton transport. The models are designed to form amphiphilic alpha helices which, in a membrane and in the presence of an applied electrical field, self-associate to form conducting helix bundles. Following design of suitable peptide sequences to allow convenient handling, covalently linked dimers of the designed sequences are prepared to probe the factors influencing channel stability, while incorporation of norvaline derivatives into specific positions of the sequences permits evaluation of their effects on the packing properties of the peptides. Membrane channels, permitting the transport of ions or small molecules, constitute one of the critical modes of communication across cell membranes. In addition, they are critical in cell regulation and mediate all electrical excitability of the nervous and muscle systems. Professor Karin S. Akerfeldt, of the Department of Chemistry at Rutgers, the State University of New Jersey, Camden Campus, with the support of a Research in Undergraduate Institutions award from the Organic Synthesis Program and the Office of Multidisciplinary Activities of the Mathematical and Physical Sciences Directorate, prepares comparatively small model polypeptides designed to serve as transmembrane ion channels. Through the synthesis and study of these model compounds, Professor Akerfeldt explores various factors influencing the flow of ions across membranes. These factors are difficult to explore with the naturally occurring channel-forming peptides given their complexity, instability in the absence of membranes, and often limited availability in significant quantities.

在有机合成计划和数学和物理科学局多学科活动办公室颁发的本科院校研究奖的支持下，新泽西州立大学校园罗格斯分校化学系的Karin S.AkerFeldt教授进行了离子通道形成肽的合成和分析。合成了结构明确的人工质子选择通道作为模型，以研究质子传输的基本机制。这些模型被设计成形成两亲性的阿尔法螺旋，这些螺旋在膜上和外加电场的存在下，自结合形成导电螺旋束。在设计合适的肽序列以便于操作之后，制备所设计序列的共价连接的二聚体以探索影响通道稳定性的因素，同时将去甲丙氨酸衍生物掺入序列的特定位置允许评估它们对肽的堆积性质的影响。膜通道，允许离子或小分子的运输，构成了跨细胞膜通讯的关键模式之一。此外，它们在细胞调节中起关键作用，并调节神经和肌肉系统的所有电兴奋性。新泽西州立大学校园罗格斯分校化学系的Karin S.AkerFeldt教授在有机合成计划和数学和物理科学委员会多学科活动办公室颁发的本科院校研究奖的支持下，制备了相对较小的模型多肽，旨在用作跨膜离子通道。通过这些模型化合物的合成和研究，艾克费尔特教授探索了影响离子跨膜流动的各种因素。这些因素很难用自然产生的通道形成肽来探索，因为它们的复杂性，在没有膜的情况下不稳定，而且往往限制了大量的可获得性。