High field NMR spectrometer for chemical biology research

大多数药物都是小的有机化合物，它们通过与生物大分子(如蛋白质或核酸)特定地相互作用并改变其功能来施加影响。未来治疗药物的多样性是巨大的；理论上可以存在的小分子的数量远远超过了可以合成和测试的数量。因此，我们用化学手段控制生命系统的能力主要受限于在浩瀚的可能性宇宙中发现合适的分子的困难。化学生物学领域试图通过研究控制大分子/药物相互作用的规则以及这些相互作用如何最终导致生理效应来应对这一挑战。这一过程中的两个关键步骤是合成新化合物和详细描述它们与生物靶标的相互作用。为了使这些步骤成功，研究人员必须能够用原子分辨率来阐明所讨论的分子结构。核磁共振光谱是一种非常强大的技术，可以确定有机化合物、生物大分子及其络合物的三维结构。我们需要核磁共振设备，以增加这一重要工具在我们研究中的可用性和多功能性。新的基础设施将用于开发生物重要化合物类的新合成路线，改进潜在应用于癌症、炎症和传染病的化学修饰的寡核苷酸，提炼细菌耐药酶的抑制剂，生产天然产品和天然产品杂交物，并研究蛋白质/药物相互作用的基本热力学原理。

Most pharmaceuticals are small organic compounds that exert their influence by specifically interacting with a biological macromolecule such as a protein or nucleic acid and altering its function. The diversity of prospective therapeutic agents is enormous; the number small molecules that can exist in theory vastly exceeds the number that can ever be synthesized and tested. Thus our ability to control living systems chemically is limited primarily by the difficulty of uncovering appropriate molecules within the immense universe of possibilities. The field of Chemical Biology seeks to meet this challenge by studying the rules that govern macromolecule/drug interactions and how these interactions lead ultimately to a physiological effect. Two critical steps in this process are the synthesis of novel compounds and detailed characterization of their interactions with biological targets. In order for these steps to be successful, researchers must be able to elucidate the structures of the molecules in question with atomic resolution.Nuclear Magnetic Resonance (NMR) spectroscopy is an extremely powerful technique for determining the three-dimensional structures of organic compounds, biological macromolecules, and their complexes. We are requesting NMR equipment that will increase the availability and versatility of this vital tool in our research. The new infrastructure will be used to develop new synthetic routes to biologically important classes of compounds, improve chemically-modified oligonucleotides with potential applications against cancer, inflammatory, and infectious diseases, refine inhibitors of a bacterial drug-resistance enzyme, generate natural products and natural product hybrids, and study the fundamental thermodynamic principles underlying protein/drug interactions.