Peptoid Macrocycles As Biomimetic Architectures

类肽大环化合物作为仿生结构

• 批准号: 2002890
• 负责人: Kent Kirshenbaum
• 金额: $ 45万
• 依托单位: New York University
• 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: 2020-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2002890&HistoricalAwards=false
• 关键词: Peptoid; Macrocycles; Biomimetic; Architectures

With support from the Macromolecular, Supramolecular, and Nanochemistry (MSN) Program in the Division of Chemistry, Professor Kirshenbaum at New York University is studying a family of “peptoid” molecules that mimic natural proteins. Peptoids are peptide-mimics but with the side chain connected to the nitrogen of the peptide backbone. Because this unique backbone structure, they often are more stable in biological systems and can be used for therapeutic applications. Professor Kirshenbaum's project explores how organizing the peptoids into cyclic structures may enable the design of new molecules with elaborate structures and valuable functions. The broader impacts of the project include collaborations with researchers on the chemical biology of cancer and creation of intellectual property for commercial development of bioactive peptidomimetics. Students contributing to the project are trained at the interface of bio-organic chemistry and biomedicine. Professor Kirshenbaum provides valuable training for a broad range of students including a project suitable for high school students. Professor Kirshenbaum makes TV appearances and appears in social media that informs the general public about the properties and functions of biological molecules. Peptoids are peptidomimetic oligomers composed of N-substituted glycine units. A variety of biomimetic properties have recently been described for peptoids. In order to further develop functional peptoids, the project is pursuing new strategies to enforce their conformational ordering. The research establish predictable relationships between the sequence, the structure, and the function of peptoid oligomers. In particular, the project explores the use of macrocyclic constraints to dictate the folding of peptoids for diverse applications. These applications include complex metal-associated, self-assembling materials and peptoid macrocycles to antagonize protein-protein interactions of biomedical importance. Establishing improved computational strategies for prediction of peptoid macrocycle structures is a critical component of the research plan. Teaching modules introduce peptidomimetic enzyme inhibitors to undergraduate biochemistry laboratory classes.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.

在化学系大分子、超分子和纳米化学（MSN）项目的支持下，纽约大学的Kirshenbaum教授正在研究一类模拟天然蛋白质的“类肽”分子。类肽是肽的模拟物，但其侧链与肽主链的氮相连。由于这种独特的骨干结构，它们通常在生物系统中更稳定，可以用于治疗应用。Kirshenbaum教授的项目探讨了如何将类肽组织成环状结构，从而设计出具有复杂结构和有价值功能的新分子。该项目的更广泛影响包括与研究人员就癌症的化学生物学进行合作，并为生物活性肽模拟物的商业开发创造知识产权。参与该项目的学生将接受生物有机化学和生物医学的交叉训练。Kirshenbaum教授为广泛的学生提供了有价值的培训，包括一个适合高中生的项目。科什鲍姆教授经常在电视和社交媒体上露面，向公众介绍生物分子的特性和功能。类肽是由n -取代甘氨酸单位组成的拟肽低聚物。最近对类肽的各种仿生特性进行了描述。为了进一步开发功能性肽，该项目正在寻求新的策略来加强它们的构象排序。本研究建立了肽类低聚物的序列、结构和功能之间可预测的关系。特别是，该项目探讨了使用大环约束来决定折叠肽的各种应用。这些应用包括复杂的金属相关，自组装材料和肽类大环，以对抗生物医学上重要的蛋白质-蛋白质相互作用。建立改进的计算策略来预测肽类大环结构是研究计划的关键组成部分。教学模块将拟肽酶抑制剂引入本科生物化学实验课。该奖项反映了美国国家科学基金会的法定使命，并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

Elaborate Supramolecular Architectures Formed by Co-Assembly of Metal Species and Peptoid Macrocycles

• DOI: 10.1021/acs.cgd.1c00209
• 发表时间: 2021-05-18
• 期刊: CRYSTAL GROWTH & DESIGN
• 影响因子: 3.8
• 作者: Jiang, Linhai;Hu, Chunhua Tony;Kirshenbaum, Kent
• 通讯作者: Kirshenbaum, Kent

Evaluating the Conformations and Dynamics of Peptoid Macrocycles

• DOI: 10.1021/acs.jpcb.2c01669
• 发表时间: 2022-07-12
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Eastwood, James R. B.;Jiang, Linhai;Renfrew, P. Douglas
• 通讯作者: Renfrew, P. Douglas