New Peptidic Foldamer Structures

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In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Professor Samuel Gellman of the University of Wisconsin at Madison will develop new oligomers with protein-like folding behavior ("foldamers"). This work will focus on the use of gamma-amino acid building blocks, to construct "gamma-peptides" that adopt novel shapes or for use in conjunction with alpha- and/or beta-amino acids to generate foldamers with more diverse backbones. The research is directed toward conformations that can ultimately be tailored to achieve specific molecular engineering goals. This experimental program includes three specific goals. One is to build upon the recent NSF-supported discovery of alpha / beta / gamma-peptides that mimic natural alpha-helices; an experimental strategy will be developed for quantifying the thermodynamics of alpha / beta / gamma-peptide folding, so that the subunits can be optimized. The second goal involves exploration of previously unknown types of gamma-amino acids as potential foldamer subunits. This effort will necessitate the development of new asymmetric synthesis methods. The third component of this program is directed toward unusual or unprecedented secondary structures (e.g., oval-shaped helices) that could ultimately be used to accomplish high-value tasks, such as mimicking expansive, information-rich surfaces on natural proteins. The broader impacts of this research will include training young scholars to be successful in highly intersciplinary and collaborative research environments, and the generation of tools can be used by many researchers to address molecular-level challenges in medicine, nanotechnology and other fields. Biological systems make heavy use of proteins to carry out complex tasks at the molecular level. Proteins are "oligomers": they are composed of multiple chemical subunits linked together in a long chain. The chain must fold into a specific, complex shape in order for the protein to become functional. This research project is part of a growing international effort, inspired by natural proteins, to create new types of synthetic oligomers that can adopt complex shapes and perform useful functions. Long-term outcomes of this basic research could include the development of new types of medicines, materials with unprecedented properties, and other useful chemical technologies.