RUI: Development of peptoids for molecular recognition in water

蛋白质是迷人的分子，可以折叠成三维结构，具有广泛的生物功能。例如，一些蛋白质折叠以产生特定大小和形状的口袋，用于识别和运输靶分子。 被称为类肽的合成的非生物分子相对容易合成，并且可以模拟蛋白质结构。圣克拉拉大学的Amelia Fuller教授和她实验室的本科生合成并研究了新型类肽，以研究它们如何折叠并与水中的其他小分子相互作用。该研究小组旨在更好地了解类肽的结构-性质关系。这种理解将为未来的拟肽设计提供信息，这些拟肽的应用范围从药物的运输到创造新的软材料，如用于组织工程、缓释药物递送系统或吸收有害物质的水凝胶。参与研究的本科生培养了他们解决问题的能力。相当一部分的研究是由学生在本科实验室课程的介绍注册。这个场地为数十名本科生提供了高影响力的教育体验，在早期阶段为他们提供了成功的科学职业所需的技术技能。与此同时，包括本科生在这项工作中产生的课程材料和教育进步被广泛传播。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，类肽在水中折叠和自缔合成三维结构是由结构单元（N-取代甘氨酸）的序列编程的。由于它们对蛋白水解的抗性，类肽对于生物医学应用是有利的。预测性设计用于所需应用的结构复杂的类肽的能力需要更好地理解序列-结构相关性。 在NSF化学部的大分子，超分子和纳米化学计划的支持下，富勒实验室的学生合成和研究具有两种设计的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物的组合阵列。 该研究项目旨在确定两亲性类肽的重要序列-结构相关性，并研究它们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，从而推动了它们作为一类新型超分子受体在水中发挥作用。该奖项反映了NSF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.