RUI: Development of peptoids for molecular recognition in water

蛋白质是一种迷人的分子，可以折叠成三维结构，具有广泛的生物功能。例如，一些蛋白质折叠形成特定大小和形状的口袋，用于识别和运输目标分子。合成的、被称为类肽的非生物分子相对容易合成，可以模拟蛋白质结构。圣克拉拉大学（Santa Clara University）的阿米莉亚·富勒（Amelia Fuller）教授和她实验室的本科生合成并研究了新型肽类物质，以研究它们如何折叠并与水中其他小分子相互作用。研究小组的目标是更好地了解肽的结构-性质关系。这一认识将为今后肽类药物的设计提供信息，这些肽类药物的应用范围从药物运输到创造新的软材料，如用于组织工程的水凝胶、缓释药物输送系统或有害物质的吸收。参与研究的本科生培养解决问题的能力。相当一部分的研究是由参加本科实验入门课程的学生进行的。这个场地为数十名本科生提供了高影响力的教育体验，使他们在早期阶段就具备了成功从事科学事业所需的技术技能。与此同时，由于将本科生纳入这项工作而产生的课程材料和教育进步也得到了广泛传播。类肽是一种模块化和可定制的仿生分子支架。与蛋白质类似，类肽在水中的折叠和自结合形成三维结构是由构建块（n -取代甘氨酸）的序列决定的。由于它们对蛋白质水解的抗性，类肽在生物医学应用中是有利的。预测设计结构复杂的肽类药物的能力需要更好地理解序列-结构的相关性。在美国国家科学基金会化学部大分子、超分子和纳米化学项目的支持下，富勒实验室的学生们用两种设计方法合成和研究了n -取代甘氨酸低聚物：两亲性螺旋分子和硫醚连接的类肽两亲性分子组合阵列。本研究项目旨在确定两亲性肽的重要序列-结构相关性，并研究其识别水中其他小分子的亲和力。这些研究阐明了类肽的重要序列和结构特征，促进了它们作为一类在水中起作用的新型超分子受体的应用。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。

Proteins are fascinating molecules that fold into three-dimensional structures for a wide range of biological functions. For example, some proteins fold to create a pocket of specific size and shape for recognition and transport of target molecules. Synthetic, abiological molecules termed peptoids are relatively easy to synthesize and may emulate protein structures. Professor Amelia Fuller at Santa Clara University and the undergraduate students in her laboratory synthesize and study novel peptoids to investigate how they fold and interact with other small molecules in water. The research team aims to better understand the structure-property relationships in peptoids. This understanding will inform future design of peptoids for applications ranging from transport of pharmaceuticals to creating new soft materials such as hydrogels for use in tissue engineering, sustained-release drug delivery systems, or absorption of harmful materials. Undergraduate students who participate in the research cultivate their problem-solving skills. A substantial fraction of the research is carried out by students enrolled in an introductory undergraduate laboratory course. This venue provides a high impact educational experiences to dozens of undergraduate students, equipping them at an early stage with technical skills needed for successful careers in science. In parallel, curricular materials and educational advances that arise from including undergraduates in this work are broadly disseminated.Peptoids are a modular and customizable biomimetic molecular scaffold. Similar to proteins, the folding and self-association of peptoids into three-dimensional structures in water are programmed by the sequence of the building blocks (N-substituted glycines). Due to their resistance to proteolysis, peptoids are advantageous for biomedical applications. The ability to predictively design structurally complex peptoids for desired applications requires a better understanding of the sequence-structure correlations. With the support of the Macromolecular, Supramolecular and Nanochemistry Program of the NSF Division of Chemistry, students in the Fuller laboratory synthesize and study N-substituted glycine oligomers with two designs: amphiphilic helical molecules and combinatorial arrays of thioether-linked peptoid amphiphiles. This research project aims to identify important sequence-structure correlations of amphiphilic peptoids and investigates their affinity for recognizing other small molecules in water. These studies clarify the important sequence and structural features of peptoids that advance their utility as a new class of supramolecular receptors that function in water.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.