CAREER: A Modular Approach to Proteomimetics

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

A primary challenge in the field of proteomimetics is the identification of building blocks that mimic key protein structural motifs while projecting functional groups in three-dimensional space for specific binding interactions with other proteomimetics, small molecules, or endogenous biopolymer targets. This project targets the use of readily accessible synthetic building blocks - di- and triisoxazolidines - to assemble molecules that will be screened for the ability to form higher order structures such as helical bundles and helix-turn-helices. As part of a broader partnership with primarily minority-serving institutions, women's colleges, and the chemical industry, a course on "Critical Thinking and Communication Skills for Scientists" will be developed and taught to entering B.S./M.S. students, focusing on the building blocks of good scientific writing, critical thinking, and critical reading and including peer review as an important component. With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Anna Mapp, of the Department of Chemistry at the University of Michigan, is exploring the synthesis and properties of molecules that mimic the structure and function of proteins. Proteins play a key role in the functions of life by acting as catalysts, structural components, signal transducers, and molecular receptors, and the function of each protein is dictated by its unique three-dimensional structure. Since the constituents of proteins became known, there has been great interest in reconstituting the structure and function of proteins with non-natural counterparts through either minor alterations of the natural components or wholesale replacement strategies. Professor Mapp is synthesizing novel non-amino acid-based scaffolds and exploring their self-assembly into more complex structures mimicking those formed by proteins, thereby gaining insight into the function and mechanism of natural enzymes and developing artificial proteins (proteomimetics) with improved function and properties relative to natural systems. In addition, the undergraduate, B.S./M.S., graduate, and postdoctoral researchers that participate in this interdisciplinary effort will be well-trained in both chemistry and biology and be prepared to make major contributions to our nation's biotechnology research effort. Professor Mapp is also playing an integral role in a B.S./M.S. program currently under development at the University of Michigan that is built upon partnerships with primarily minority-serving institutions, women's colleges, and chemical industry.