Membrane transport systems

这项研究的目标是设计简单的化学系统，复制和改善所有细胞生命中发现的膜运输功能。 在过去的十年中，该计划已经产生了广泛的新化合物和化学系统，这些化合物和化学系统再现了天然离子通道的许多基本功能。 现在可以通过常规的溶液和固相合成，使用离子通道候选物的简化和快速合成来设计和制备与天然实例一样活性的合成化合物。 提出的研究计划面临的实际和基本的挑战，在膜运输系统的设计和组装。 新的合成产生了新的活性化合物的机制研究，这将证明新类型的调节离子转运。 在一个平行的轨道，我们已经探讨了一些例子，其中离子通道已形成通过定向自组装合适的组件。 产生的渠道是前所未有的，复杂的，非常具有挑战性的研究。 无论它们的结构是什么，现在很清楚的是，激发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匀溶液中发生，并提出扩展来处理双层膜相中遇到的充满活力的复杂性。 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。 下一个实际的目标是一个稳定的和支持的双层膜最初为我们自己使用的新的转运蛋白的表征。 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.