Membrane transport systems

这项研究的目标是设计简单的化学系统，复制和改进在所有细胞生命中发现的膜运输功能。这一计划已经产生了一系列新的化合物和化学体系，它们再现了天然离子通道的许多基本功能。现在，通过传统的溶液和固相合成，使用离子通道候选者的简化和快速合成，可以设计和制备与自然例子一样活跃的合成化合物。在膜传输系统的设计和组装方面，所提出的研究计划面临着实际和根本的挑战。由于新的合成方法产生了用于机理研究的新的活性化合物，并将展示新类型的受调控的离子传输。在平行的轨道上，我们已经探索了一些通过适当组件的定向自组装形成离子通道的例子。但产生的通道是史无前例的、复杂的，研究起来非常具有挑战性。无论它们的结构如何(S)，现在很清楚，激励最初努力的简单设计思想太天真了。我们已经开发了热力学模拟来分析和预测自组装过程如何在均相溶液中发生，并提出了扩展来处理在双层膜阶段遇到的能量复杂性。在技术层面上，我们继续开发技术来处理和注入几千个通道形成分子到双层膜中。我们的下一个实际目标是稳定和支撑的双层膜，最初是为了我们自己用于表征新的转运体。如果这是成功的，传感器应用将是可能的。

The goal of this research is to design simple chemical systems that reproduce and improve upon the membrane transport functions found in all cellular life.  In the last decade, this program has produced a wide array of new compounds and chemical systems that have reproduced many basic functions of natural ion channels.  It is now possible to design and prepare synthetic compounds that are as active as natural examples using simplified and rapid syntheses of ion channel candidates through conventional solution and solid-phase synthesis.  The program of research proposed confronts both practical and fundamental challenges in the design and assembly of membrane transport systems.  The new syntheses have produced new classes of active compounds for mechanistic investigation and which will demonstrate new types of regulated ion transport.  In a parallel track, we have explored some examples in which ion channels have been formed through directed self-assembly of suitable components.  The channels produced are unprecedented, complex, and very challenging to study.  Whatever their structure(s), is clear now that the simple design ideas that motivated the initial effort are too naïve.  We have developed thermodynamic simulations to analyze and predict how self-assembly processes occur in homogeneous solution, and propose extensions to deal with the energetic complexities encountered in the bilayer membrane phase.  On a technical level, we continue to develop techniques to handle and inject a few thousand channel-forming molecules into bilayer membranes.   The next practical target is a stabilized and supported bilayer membrane initially for our own use in the characterization of new transporters.  To the extent that this is successful, sensor applications will be possible.