RUI: Synthesis, Structural and Functional Studies of Bioinspired Macrocyclic Oligoamides

在这项由化学系化学结构、动态和机制B项目资助的本科生研究机构(RUI)项目中，圣克拉拉大学化学和生物化学系的Amelia Fuller教授正在研究模仿自然界中发现的化合物的大分子的合成和性质。制造这些化合物的合成方法使富勒教授能够很容易地改变结构和化学成分，最终能够比较分子功能上的这些变化。研究了这些分子的三维结构及其与金属离子的结合能力。这些分子在治疗和传感器方面具有潜在的应用前景。实验由本科生在两个地点进行：在富勒教授的独立实验室和在圣克拉拉大学的本科生有机实验室入门课程。将研究经验整合到课程课程中，加强了大约50名本科生在颁奖过程中的科学培训。大环肽类天然产物作为潜在的治疗药物、超分子宿主和金属结合剂具有广泛的应用前景。这些都启发了不同官能化的大环N-取代寡酰胺的设计、合成和研究。这些合成方法提供了多种大环的途径，包括寡酰胺主链中的氮杂环或碳环芳环。要制备的实例调制附加官能度、环大小和环柔性，所有这些都有望提供有趣的构象和功能贡献。研究了它们在溶液和固体中的结构。评价了含唑大环与金属结合的能力，类似于含唑多肽衍生的天然产物。

In this Research at Undergraduate Institutions (RUI) project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Amelia Fuller of the Department of Chemistry and Biochemistry at Santa Clara University is studying the synthesis and properties of large molecules that mimic compounds found in nature. The synthetic methods to make these compounds allow Professor Fuller to easily change structure and chemical composition, ultimately enabling a comparison of these variations on molecular function. The three-dimensional structures of these molecules and their abilities to bind to metal ions is studied. These molecules have potential application as therapeutics and sensors. Experiments are being conducted by undergraduate students in two venues: in Professor Fuller's independent laboratory, and in an introductory undergraduate organic laboratory course at Santa Clara University. Integration of research experiences into the course curriculum enhances the scientific training of approximately 50 undergraduate students over the course of the award. Macrocyclic peptide-derived natural products exhibit a range of applications as potential therapeutics, supramolecular hosts, and metal-binding agents. These inspire the design, synthesis, and study of diversely functionalized macrocyclic N-substituted oligoamides. The syntheses provides access to diverse macrocycles that include either azole heterocycles or carbocyclic aromatic rings in the oligoamide backbone. Examples to be prepared modulate appended functionality, ring size, and ring flexibility, all of which are anticipated to confer interesting conformational and functional contributions. Their structures are investigated in solution and in the solid state. The capacity of azole-containing macrocycles to bind metals in analogy to azole-containing peptide-derived natural products is evaluated.