Peptoid Macrocycles As Biomimetic Architectures

在化学系大分子、超分子和纳米化学(MSN)计划的支持下，纽约大学的Kirshenbaum教授正在研究一种模仿天然蛋白质的“类肽”分子家族。类肽是多肽的模拟物，但侧链连接到多肽骨架的氮上。由于这种独特的骨架结构，它们在生物系统中往往更稳定，可以用于治疗应用。Kirshenbaum教授的项目探索了如何将肽类化合物组织成环状结构，从而能够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在癌症化学生物学方面的合作，以及为生物活性多肽仿制药的商业开发创造知识产权。为该项目做出贡献的学生在生物有机化学和生物医学的交汇点上接受培训。Kirshenbaum教授为广泛的学生提供有价值的培训，包括一个适合高中生的项目。Kirshenbaum教授经常在电视上露面，并出现在社交媒体上，向公众宣传生物分子的特性和功能。类肽是由N-取代甘氨酸单元组成的类肽低聚物。最近已经描述了类肽的各种仿生特性。为了进一步开发功能性类肽，该项目正在寻求新的策略来加强它们的构象有序。这项研究建立了类肽低聚体的序列、结构和功能之间的可预测关系。特别是，该项目探索了大环限制条件的使用，以规定不同应用中的类肽折叠。这些应用包括复杂的金属相关的自组装材料和类肽大环，以对抗具有生物医学意义的蛋白质-蛋白质相互作用。建立用于预测类肽大循环结构的改进的计算策略是研究计划的关键组成部分。教学单元将肽类酶抑制剂引入本科生物化学实验室课程。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.