Molecular balance for measuring molecular-level anion effects on amino acids

用于测量分子水平阴离子对氨基酸影响的分子平衡

• 批准号: 1310139
• 负责人: Ken Shimizu
• 金额: $ 39万
• 依托单位: University of South Carolina at Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1310139&HistoricalAwards=false
• 关键词: Molecular; balance; measuring; molecular; level

In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Ken Shimizu of the University of South Carolina will study the ability of anions to stabilize and destabilize protein structures. The strategy is use a "molecular balance," a small molecule model system that can measure and provide molecular-level insight into the interactions of anions with individual amino acid side chains. These molecular balances are in equilibrium between folded and unfolded conformers. In the folded conformers, amino acid side-chains in the balances form intramolecular hydrophobic and non-covalent interactions with a hydrophobic aromatic shelf. In the unfolded conformers, these intramolecular interactions are broken. Thus, the influence of anions on these non-covalent interactions can be quantitatively measured by monitoring the folded/unfolded ratios using NMR spectroscopy. The balances are assembled in a modular fashion, allowing the rapid synthesis of a series of balances containing different amino acid side chains, water solubilizing groups, and various hydrophobic surfaces. The proposed balances also contain fluorine NMR labels that provide more accurate measurements and enable their study within complex heterogeneous environments. The broader scientific impact of this project will be the development of new strategies and methods for stabilizing and solubilizing proteins. Additional activities pursued during this project will be: 1) to develop a free website to help undergraduate students to study organic chemistry, 2) to provide research opportunities for groups underrepresented in chemistry, and 3) to perform chemistry demonstrations at area K-6 classes and to participate in the SCienceLab program that brings middle and high school classes to the university for a hands-on laboratory experience. Proteins are biological molecules that perform critical structural and active functions in biological systems. These studies will provide molecular-level insights into how proteins and segments of proteins interact with each other as well as how the fold into complex structures. A net result of this research will be to enable new strategies and methods for stabilizing and solubilizing proteins. Such work will have applications in enhancing the shelf lives of protein- and antibody-based pharmaceuticals and as well as assisting in the development of biosensors and new pharmaceuticals.

在这个由化学部的大分子，超分子和纳米化学计划资助的项目中，南卡罗来纳大学的Ken Shimizu将研究阴离子稳定和破坏蛋白质结构的能力。该策略是使用“分子平衡”，这是一个小分子模型系统，可以测量和提供分子水平的见解，以了解阴离子与单个氨基酸侧链的相互作用。这些分子平衡在折叠和展开的构象异构体之间处于平衡状态。在折叠的构象异构体中，平衡中的氨基酸侧链与疏水芳香族架子内分子内疏水和非共价相互作用。在展开的构象异构体中，这些分子内相互作用被损坏。因此，可以通过使用NMR光谱法监测折叠/展开的比率来定量测量阴离子对这些非共价相互作用的影响。平衡以模块化的方式组装，从而可以快速合成一系列含有不同氨基酸侧链，水溶性基团和各种疏水表面的平衡。所提出的余额还包含氟NMR标签，可提供更准确的测量，并在复杂的异质环境中进行研究。 该项目的更广泛的科学影响将是开发稳定和溶解蛋白质的新策略和方法。 该项目期间从事的其他活动将是：1）开发一个免费的网站，以帮助本科生学习有机化学，2）为化学中人数不足的团体提供研究机会，以及3）在K-6区域进行化学演示，并参加ScienceLab计划，并参加ScienceLab计划，以使中学和高中班级为实施实验室的实验室经验。 蛋白质是在生物系统中执行关键结构和活性功能的生物分子。 这些研究将提供分子水平的见解，以了解蛋白质的蛋白质和蛋白段如何相互相互作用以及如何折叠成复杂的结构。 这项研究的净结果将是实现稳定和溶解蛋白质的新策略和方法。此类工作将应用于增强基于蛋白质和抗体的药物的保质期，并协助开发生物传感器和新药。