CAREER: Fostering Innovative Scientists Through Development of Biomimetic Catalysts for Discovery of New Medicines.

职业：通过开发仿生催化剂来发现新药物，培养创新科学家。

• 批准号: 1752912
• 负责人: Benjamin Gorske
• 金额: $ 51.2万
• 依托单位: Bowdoin College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1752912&HistoricalAwards=false
• 关键词: CAREER; Fostering; Innovative; Scientists; Through

Life is one of the most powerful forces shaping our planet. Thus, mimicking the molecules of life (one of the NSF "Grand Challenges" for 21st century science) presents an opportunity to controllably harness this power to benefit humanity. Currently, many medicines are adaptations of molecules produced by living organisms. By constructing artificial analogs of the enzymes that Nature uses to build molecules, new potential medicines may be discovered. In this project, Dr. Gorske is developing enzyme mimics to accomplish this goal. The design of these enzyme mimics is allowing undergraduates to construct them with minimal training. This is enabling students to gain experience conducting meaningful research prior to choosing a major. Such early access to these research experiences, which include both summer research internships and course-related laboratories, is stimulating interest in pursuing science as a career. Especially, underprepared and underrepresented students and groups are being exposed to STEM fields. In the process, students are contributing directly to the development of new technology for facilitating the discovery of urgently needed medicines.With support from the Chemical Catalysis Program of the Chemistry Division, Dr. Gorske of Bowdoin College is developing biomimetic catalysts for nucleophilic trifluoromethylations that deliver enantiopure alpha-trifluoromethyl alcohol and beta-trifluoromethyl carbonyl subunits for construction of new biological probes and medicines. These studies are elucidating the structural design parameters of peptidomimetic catalysts that maintain their competency in polar solvents and facilitate nucleophilic trifluoromethylation reactions. In turn, the results of these investigations are informing iterative cycles of catalyst design and structure-activity relationship analysis that aim to produce highly enantio- and regio-selective nucleophilic trifluoromethylation catalysts with wide substrate scope. More broadly, a new class of structured catalyst scaffolds designed to be generally applicable to a wide range of reactions is being realized, while simultaneously providing early but authentic research experiences for undergraduates. These experiences are specifically designed to enhance learning outcomes and enthusiasm for pursuit of STEM careers, especially among members of underrepresented groups in STEM fields that are identified through partnerships with both internal and local external organizations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生命是塑造我们星球的最强大的力量之一。因此，模仿生命分子（美国国家科学基金会对21世纪世纪科学的“重大挑战”之一）提供了一个机会，可以可控地利用这种力量造福人类。目前，许多药物都是由生物体产生的分子改编而成的。通过构建大自然用来构建分子的酶的人工类似物，可能会发现新的潜在药物。在这个项目中，Gorske博士正在开发酶模拟物来实现这一目标。这些酶模拟物的设计允许大学生用最少的训练来构建它们。这使学生能够在选择专业之前获得进行有意义研究的经验。这种抢先体验这些研究经验，其中包括夏季研究实习和课程相关的实验室，是刺激兴趣追求科学作为一种职业。特别是，准备不足和代表性不足的学生和团体正在接触STEM领域。在此过程中，学生们直接为新技术的开发做出贡献，以促进急需药物的发现。在化学系化学催化计划的支持下，鲍登学院的Gorske博士正在开发亲核三氟甲基化的仿生催化剂，提供对映体纯的α-三氟甲基醇和β-三氟甲基羰基亚基，用于构建新的生物探针和药物。这些研究阐明了肽模拟物催化剂的结构设计参数，这些催化剂保持其在极性溶剂中的能力并促进亲核三氟甲基化反应。反过来，这些调查的结果是通知催化剂设计和结构-活性关系分析，旨在生产高对映体和区域选择性亲核三氟甲基化催化剂与广泛的底物范围的迭代循环。更广泛地说，一种新的结构化催化剂支架正在实现，其设计通常适用于广泛的反应，同时为本科生提供早期但真实的研究经验。这些经验是专门为提高学习成果和追求STEM事业的热情而设计的，特别是通过与内部和当地外部组织的合作伙伴关系确定的STEM领域代表性不足的群体的成员。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。