RUI: Development of peptoids for molecular recognition in water

Santa Clara University, Santa Clara CA

Investigators

Abstract

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.