Novel Approaches to Modifications of Nucleosides and Related Heterocycles

核苷和相关杂环化合物修饰的新方法

• 批准号: 1953574
• 负责人: Mahesh Lakshman
• 金额: $ 49万
• 依托单位: CUNY City College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1953574&HistoricalAwards=false
• 关键词: Novel; Approaches; Modifications; Nucleosides; Related

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Mahesh K. Lakshman in the Department of Chemistry & Biochemistry at The City College of New York. Professor Lakshman is working with graduate and undergraduate students to develop ways to modify nucleosides, which are molecules that are the building blocks of DNA and RNA. Modified nucleosides are important because they are used in medicinal applications, as plant cell growth stimulants, and as probes for understanding biological processes. Nucleosides consist of two linked parts: a sugar and a base pair. This program is focused on determining how to use a mild oxidant to change the structure of the base pair and to attach the base pair to the sugar portion of the nucleoside. Since nucleosides have many reactive parts, these studies are determining how to control the modification procedures to give a single product. This work is also establishing a fundamental understanding of the reactivity of mild oxidants with nucleosides. Professor Lakshman’s research group is ethnically and gender diverse, contributing to the diversity of the future workforce. These students obtain professional hands on experience in planning, developing, and performing chemical reactions, as well as soft skills such as teamwork, oral and written dissemination of scientific information, and communication abilities. Professor Lakshman has been associated with significant research infrastructure development and outreach activities, where the latter has providedyoung students with hands-on experience in science. It also allows for parents to interact with faculty and to understand the role of science, which serves to better a general understanding and perception of science, education, and research, and their impact on society.Nucleosides are an important class of biomolecule due to their presence in all living systems. Modified nucleosides have been developed for medicinal purposes in the control of cancer and viral diseases, as detection tools, and as probes of biochemical and biological processes. The development of new ways to synthesize unknown nucleoside structures will provide access to new applications. Professor Lakshman is developing oxidative coupling processes to modify purine and pyrimidine nucleosides and to connect base pairs to sugars. This project is using iodonium reagents to achieve these transformations and is applying fundamental reactivity studies to determine trends that will facilitate the prediction of selectivity. These studies are overcoming challenges with nucleoside modification due to the inherent reactivity of these compounds. Professor Lakshman’s diverse research group includes students at all educational levels (Ph.D., MS, 5-year BS-MS, and BS).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.

有了这个奖项，美国国家科学基金会化学部的化学合成计划正在支持Mahesh K.拉克什曼在纽约城市学院化学生物化学系。Lakshman教授正在与研究生和本科生合作，开发修饰核苷的方法，核苷是DNA和RNA的构建单元。修饰的核苷是重要的，因为它们用于医药应用，作为植物细胞生长刺激剂，并作为探针用于了解生物过程。核苷由两个相连的部分组成：糖和碱基对。这个程序的重点是确定如何使用温和的氧化剂来改变碱基对的结构，并将碱基对连接到核苷的糖部分。由于核苷具有许多反应性部分，这些研究正在确定如何控制修饰程序以得到单一产物。这项工作也建立了对温和氧化剂与核苷反应性的基本认识。教授拉克什曼的研究小组是种族和性别多元化，有助于未来劳动力的多样性。这些学生获得规划，开发和执行化学反应的专业实践经验，以及团队合作，口头和书面传播科学信息和沟通能力等软技能。 拉克什曼教授一直与重大的研究基础设施的发展和推广活动，后者提供了dyesterday学生在科学实践经验。它还允许家长与教师互动，了解科学的作用，这有助于更好地理解和科学，教育和研究的整体看法，以及它们对社会的影响。核苷是一类重要的生物分子，因为它们存在于所有生命系统中。修饰的核苷已被开发用于控制癌症和病毒性疾病的医学目的，作为检测工具，以及作为生物化学和生物学过程的探针。合成未知核苷结构的新方法的开发将提供新的应用途径。Lakshman教授正在开发氧化偶联过程，以修饰嘌呤和嘧啶核苷，并将碱基对连接到糖。该项目正在使用碘鎓试剂实现这些转化，并正在应用基础反应性研究来确定有助于预测选择性的趋势。由于这些化合物的固有反应性，这些研究正在克服核苷修饰的挑战。教授拉克什曼的多元化研究小组包括学生在所有教育水平（博士，MS、5年制BS-MS和BS）。该奖项反映了NSF的法定使命，并且通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Cross-dehydrogenative coupling of ethers and amides with tautomerizable quinazolinones and mechanistic studies

醚和酰胺与可互变喹唑啉酮的交叉脱氢偶联及机理研究

• DOI: 10.1039/d2ob00874b
• 发表时间: 2022
• 期刊: Organic & Biomolecular Chemistry
• 影响因子: 3.2
• 作者: Sebastian, Dellamol;Willoughby, Patrick H.;Lakshman, Mahesh K.
• 通讯作者: Lakshman, Mahesh K.

Diversely C8-functionalized adenine nucleosides via their underexplored carboxaldehydes

通过未充分研究的甲醛实现不同 C8 功能化的腺嘌呤核苷

• DOI: 10.1039/d1cc06686b
• 发表时间: 2022
• 期刊: Chemical Communications
• 影响因子: 4.9
• 作者: Akula, Hari K.;Bae, Suyeal;Pradhan, Padmanava;Yang, Lijia;Zajc, Barbara;Lakshman, Mahesh K.
• 通讯作者: Lakshman, Mahesh K.