Foldamers with Heterogeneous Backbones

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

The objective of this work is to prepare foldamers (unnatural oligomers or biopolymers) that adopt defined and predictable conformations. They will synthesize and conformationally analyze a number of heterogeneous oligomers where one type of monomer (such as alpha amino acids) provides functional diversity while another type of monomer (cyclically constrained beta or gamma amino acids) provides conformational specificity and stability. Homogeneous oligomers containing just gamma amino acids will also be synthesized and analyzed as will oligomers that are heterogeneous due to monomer stereochemistry variations. Once new oligomers are identified that adopt specific conformations in aqueous solutions, they will be tested for stability to proteolytic degradation and for their ability to move across membranes of living cells. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Samuel H. Gellman of the Department of Chemistry at the University of Wisconsin. Dr. Gellman will explore the synthesis of new proteins using combinations of natural and unnatural amino acids. These proteins will then be screened to look for those which adopt specific conformations (shapes) in aqueous (water based) solutions. Those which do fold into specific and predictable shapes will be screened for their affinity to biomolecular targets. In particular, they will be screened for their ability to disrupt other protein-protein interactions. Controlled disruption of protein-protein interactions has possible future biomedical science applications in cancer prevention. Students trained as a result of working on this project will gain experience in bioorganic and supramolecular organic chemistry, hence they will have skills needed by the pharmaceutical and speciality chemicals industries.