Synthesis and Evaluation of Alkaloids to Probe Membrane Receptors - Predoctoral Supplement

扰乱膜受体功能的新小分子的发现，如G- 蛋白质偶联受体(GPCRs)和配体门控离子通道(LGIC)仍然是关键 对研究和改善人类健康具有重要意义。天然产品，特别是生物碱， 特别适合于这项任务，因为它们的结构复杂性和独特的 行动使它们成为卓越的化学探针和药物发现的极佳起点。这个 莱利实验室专注于开发步骤经济的合成路线和强大的分离方案 获取这些复杂的天然产物并将其用作研究GPCRs的药理学工具 和LGIC。这项研究使用了当代有机化学策略和尖端技术 受体药理学中回答重要生物医学问题的技术 后果。因此，莱利实验室的研究是研究生的肥沃训练场 有兴趣从事药物化学和制药科学的职业。在这 家长奖励的行政补充R35GM147005，我们要求额外的资金 支持Ana Lopez-Hernandez的研究、培训和职业发展。安娜的研究 培训是家长奖励的一个组成部分，与综合和评价 Aristotelia生物碱，抑制烟碱型乙酰胆碱受体(NAChRs)，LGIC家族。 这项研究将专注于开发一个简化的平台，以快速生成、评估和 基于具有高选择性的单个nAChR的芳基喹啉支架设计化合物 子类型。帮助安娜实现她长期的职业目标--在生物技术公司获得一个职位 作为药物发现领域的一家公司，我们已经包括了其他活动来鼓励ANA 职业发展。安娜将有机会提高她的科学能力 沟通技巧，培养她的领导能力，并在 生物技术产业。研究、培训和职业发展计划一起，它有 根据量身定做和不断发展的个人发展计划制定，将使ANA能够 以她雄厚的科学基础为基础，成为生物医学的成功一员 劳动力。

The discovery of new small molecules that perturb the function of membrane receptors, like G- protein coupled receptors (GPCRs) and ligand-gated ion channels (LGIC), remains critically important to the study and improvement of human health. Natural products, specifically alkaloids, are particularly well-suited for this task, as their structural complexity and unique mechanism of action make them superior chemical probes and excellent starting points for drug discovery. The Riley lab is focused on developing step-economic synthetic routes and robust isolation protocols to access these complex natural products and use them as pharmacological tools to study GPCRs and LGICs. This research employs contemporary organic chemistry strategies and cutting-edge techniques in receptor pharmacology to answer questions with important biomedical consequences. As such, research in the Riley lab is a fertile training ground for graduate students interested in pursuing careers in medicinal chemistry and the pharmaceutical sciences. In this administrative supplement to parent award R35GM147005, we are requesting additional funds to support the research training and career development of Ana Lopez-Hernandez. Ana’s research training is an integral component of the parent award related to the synthesis and evaluation of Aristotelia alkaloids that inhibit the nicotinic acetylcholine receptors (nAChRs), a family of LGICs. This research will focus on developing a streamlined platform to rapidly generate, evaluate, and design compounds based on the aristoquinoline scaffold with high selectivity for individual nAChR subtypes. To help Ana achieve her long-term career goal of obtaining a position at a biotechnology company in the drug discovery sector, we have included additional activities to encourage Ana’s professional development. Ana will be given opportunities to enhance her scientific communication skills, build her leadership abilities, and gain invaluable experience in the biotechnology industry. Together, the research training and career development plan, which has been crafted based on a tailored and evolving Individual Development Plan, will enable Ana to build on her strong scientific foundation and become a successful member of the biomedical workforce.