The Crotylation Way to Glycomimetics

糖模拟学的巴豆化方法

• 批准号: 1900509
• 负责人: David Mootoo
• 金额: $ 48.5万
• 依托单位: CUNY Hunter College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900509&HistoricalAwards=false
• 关键词: Crotylation; Way; Glycomimetics

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor David Mootoo of Hunter College of The City University of New York, on the synthesis and applications of carbohydrate and carbohydrate-like molecules (termed glycomimetics). Carbohydrates are involved in many biological functions including: tissue development, intracellular signaling, immune responses, cell-cell communication, cancer, metabolic disorders and pathogen infection. Understanding how carbohydrates are made and how they react adds to fundamental knowledge in cellular and molecular biology and provides insight across a variety of fields. In this context, there is a growing demand to make specific and diverse glycomimetics and to study their reactivities. While gycomimetics are desirable synthetic products, their structures are difficult to make because of their complexity. To this end, this research is developing robust methods for the synthesis of glycomimetics. This program links real-life problems in biology to chemistry solutions, thereby drawing students to the physical sciences and providing broad-based training for STEM careers. Professor Mootoo leverages potential applications to human health, the diverse 20,000-student body of Hunter College, and the unique cultural environment in New York City, to attract underrepresented high school and undergraduate students to STEM fields and the scientific workforce. The synthetic chemistry under investigation centers on the reactions of carbohydrate-derived crotylating agents with aldehydes and imines. While crotylating reagents are widely used in organic synthesis, carbohydrate variants have not been as extensively explored because of the high intrinsic reactivity of crotylating agents and the complexity and nuanced chemistry of carbohydrates. These issues are being mitigated by recent advances in organic synthesis and the expertise of Professor Mootoo in carbohydrate chemistry. A toolbox of tin, boron and silicon based reagents is being assembled and used to synthesize mimetics of biologically active glycosphingolipids and complex oligo-mannosides. The broader scientific impacts of this research include a better understanding of the immunological properties and anti-viral activities of these materials, including their role in communicable diseases. Given the often idiosyncratic reactivity of carbohydrates, this project is also unveiling unique reactivity profiles that can inform innovative paradigms for complex molecule synthesis. Finally, the research also provides excellent training for the graduate students and undergraduates that will work on this project alongside Professor Mootoo.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，NSF化学部的化学合成计划正在支持纽约城市大学亨特学院的大卫·穆图教授关于碳水化合物和碳水化合物样分子（称为糖模拟物）的合成和应用的研究。碳水化合物参与许多生物学功能，包括：组织发育、细胞内信号传导、免疫应答、细胞间通讯、癌症、代谢紊乱和病原体感染。了解碳水化合物是如何产生的，以及它们如何反应，增加了细胞和分子生物学的基础知识，并提供了跨多个领域的见解。在这种情况下，有一个不断增长的需求，使具体的和多样化的糖模拟物，并研究其反应性。 虽然仿糖剂是理想的合成产物，但由于其复杂性，其结构难以制备。为此，本研究正在开发用于合成糖模拟物的稳健方法。该计划将生物学中的现实问题与化学解决方案联系起来，从而吸引学生进入物理科学，并为STEM职业提供广泛的培训。Mootoo教授利用人类健康的潜在应用，亨特学院的20，000名学生的多元化，以及纽约市独特的文化环境，吸引代表性不足的高中和本科学生到STEM领域和科学劳动力。研究的合成化学集中在碳水化合物衍生的巴豆基化剂与醛和亚胺的反应。虽然巴豆化试剂广泛用于有机合成，但由于巴豆化试剂的高固有反应性以及碳水化合物的复杂性和细微差别的化学性质，碳水化合物变体尚未被广泛探索。有机合成的最新进展和Mootoo教授在碳水化合物化学方面的专业知识正在缓解这些问题。锡、硼和硅基试剂的工具箱正在组装，并用于合成具有生物活性的鞘糖脂和复合寡甘露糖苷的模拟物。这项研究的更广泛的科学影响包括更好地了解这些材料的免疫特性和抗病毒活性，包括它们在传染病中的作用。鉴于碳水化合物通常具有特殊的反应性，该项目还揭示了独特的反应性特征，可以为复杂分子合成提供创新范例。最后，该研究还为将与Mootoo教授一起从事该项目的研究生和本科生提供了出色的培训。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。

项目成果

Glycopolymer Microarrays with Sub‐Femtomolar Avidity for Glycan Binding Proteins Prepared by Grafted‐To/Grafted‐From Photopolymerizations

通过 Grafted–To/Grafted–From 光聚合制备的糖聚合物微阵列，对聚糖结合蛋白具有亚飞摩尔亲和力

• DOI: 10.1002/anie.202105729
• 发表时间: 2021
• 期刊: Angewandte Chemie International Edition
• 作者: Valles, Daniel J.;Zholdassov, Yerzhan S.;Korpanty, Joanna;Uddin, Samiha;Naeem, Yasir;Mootoo, David R.;Gianneschi, Nathan C.;Braunschweig, Adam B.
• 通讯作者: Braunschweig, Adam B.