Upgrade of a Campus NMR Facility for Biological Solids

描述（由申请人提供）：我们建议升级现有的600 MHz Bruker AVANCE液态核磁共振光谱仪，以对生物固体进行NMR。目前的机器（1岁）和额外要求的设备将成为大学的分析化学仪器设施（ACIF）的一部分。固体核磁共振已成为化学、生物化学、材料科学和生物物理学中广泛的药物系统的基本表征方法。本提案中提出的各种项目证明了它在大学内的巨大影响。特别是，Michael Dunn和Len Mueller将研究与色氨酸合酶的位点结合的共价中间体，Michael Pirrung将表征固相合成口服胰岛素模拟物，Katie DeFea和Len Mueller将确定PAR-2激动剂的固态结构，Chris Reed将研究无机和有机化学中的活性阳离子。这些问题都有一个共同的需要固态表征。虽然设备齐全的液态核磁共振，目前还没有大学范围内的设施能够在UCR固态核磁共振。因此，固态核磁共振设备将填补一个明显的空白，在类型的核磁共振表征，可以在加州大学滨江。 相关性：结构和生物活性之间的关系推动了治疗药物的发展。在这里，我们建议通过固态磁共振增加一个显着的分子成像能力。我们的目标是确定控制药物和靶分子之间相互作用的分子水平细节，并建立我们设计新的下一代治疗方法的化学直觉。

DESCRIPTION (provided by applicant): We propose to upgrade an existing 600 MHz Bruker AVANCE liquid-state nuclear magnetic resonance spectrometer to perform NMR on biological solids. The current machine (1-year old) and the additionally requested equipment will become part of the University's Analytical Chemistry Instrumentation Facility (ACIF). Solid-state NMR has become an essential method of characterization for a wide range of medicinal systems in chemistry, biochemistry, materials science and biophysics. Its large impact within the University is witnessed by the diversity of projects put forth in this proposal. In particular, Michael Dunn and Len Mueller will study covalent intermediates bound to the ¿-site of tryptophan synthase, Michael Pirrung will characterize solid-phase synthetic oral insulin mimics, Katie DeFea and Len Mueller will determine the solid-state structure of PAR-2 agonists, and Chris Reed will investigate reactive cations in inorganic and organic chemistry. These problems all share a common need for solid-state characterization. Although well equipped for liquid-state NMR, there are currently no University-wide facilities capable of solid-state NMR at UCR. As such, solid-state NMR equipment will fill a noticeable void in the types of NMR characterization that can be performed at UC Riverside. Relevance: The relationship between structure and biological activity drives the development of therapeutic agents. Here we propose to add a significant molecular imaging capability through solid-state magnetic resonance. The goal is to determine the molecular level details that govern the interaction between drug and target molecules and build our chemical intuition for designing novel, next-generation treatments.