International Collaboration in Chemistry: Exploring the interactions between small molecules and biopolymers using localized surface plasmon resonance (LSPR) spectroscopy

有了这个奖项，化学部的生命过程化学项目资助了加州大学圣地亚哥分校的Yitzhak Tor博士，利用基于金岛的局部等离子体换能器，探索小分子和大型生物聚合物与细胞表面成分之间的相互作用，作为化学国际合作的一部分。 作为概念验证，这种无标记方法将用于评估氨基糖苷类抗生素及其衍生物对核糖体解码位点RNA的亲和力和选择性，核糖体解码位点RNA是降低蛋白质生物合成保真度的关键识别事件。选择该系统是由于其基本意义，因为它说明了低分子量配体能够干预大型生物机器的关键功能的事实。拟议的研究将阐明与人类竞争靶相比，控制配体对细菌RNA选择性的分子特征。此外，推进所提出的平台技术将有助于方便地、无标记地探索各种大分子识别事件，其中低分子量配体影响关键大分子的折叠和功能。小分子能够干扰关键细胞成分的功能，例如核糖体，所有蛋白质都是在核糖体中合成的。 为了了解所涉及的分子相互作用，将推进一种基于专门光学技术的新技术，其中生物靶标不需要修改或改变。通过这种方式，可以快速积累关于小分子与不同生物靶标相互作用的信息。 这一追求将使研究生和博士后获得不同科学学科的培训，从合成技术到表面化学。该项目还将纳入一个推广计划，向UCSD Preuss学校的高中生介绍化学和生物学的基本原理。 简单的实验室实验和演示将开发，以说明修改表面的过程中，通过自组装？设计师？分子和使用简单的光学仪器监测生物识别事件。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Yitzhak Tor from the University of California, San Diego, to explore the interactions between small molecules and large biopolymers and cell surface components, using gold island-based localized plasmon transducers, as part of an International Collaboration in Chemistry. As a proof-of-concept, this label-free method will be used to assess the affinity and selectivity of aminoglycoside antibiotics and their derivatives to the ribosomal decoding site RNA, a key recognition event that lowers the fidelity of protein biosynthesis. This system has been selected due to its fundamental significance, as it illustrates the fact that low molecular weight ligands are capable of meddling with a critical function of a large biological machine. The proposed research will shed light on the molecular features that govern the selectivity of the ligands selectivity toward the bacterial RNA, when compared to the human competing targets. Furthermore, advancing the proposed platform technology will facilitate a convenient, label-free exploration of diverse macromolecular recognition events where low molecular weight ligands influence the folding and function of key macromolecules. Small molecules are capable of interfering with the function of critical cellular components, such as the ribosome, where all proteins are synthesized. To learn about the molecular interactions involved, a new technology based on a specialized optical technique will be advanced, where the biological targets do not need to be modified or altered. In this fashion, information about the interaction of small molecules with diverse biological targets can be accumulated rapidly. This pursuit will allow graduate students and postdoctoral fellows to acquire training in diverse scientific disciplines, ranging from synthetic techniques to surface chemistry. This project will also be integrated into an outreach program to introduce high school students at the UCSD Preuss School to basic principles of chemistry and biology. Simple lab experiments and demonstrations will be developed to illustrate the process of modifying surfaces by self-assembling ?designer? molecules and monitoring biorecognition events using straightforward optical instrumentation.