Entry Date:
August 11, 2011

Biological Properties of Mirror Image Proteins

Principal Investigator Brad Pentelute


Professor Pentelute's lab will study the biological properties of D- proteins, which are yet to be fully elucidated. D-proteins are the mirror images of the natural occurring L-proteins and can only be made by total chemical synthesis. D-proteins are thought to be non-immunogenic and resistant to proteolysis thereby making them attractive for biological and therapeutic investigation. A major problem in biomedicine is the need for protein scaffolds that mimic antibodies (bind targets with high-affinity and specificity), but are small, stable, long-lived, and non-immunogenic. The lab will chemically synthesize different D-proteins and determine their immunogenicity and pharmacokinetics. Once the superior biological properties of D-proteins have been demonstrated, a combinatorial library of D-monobodies (D-protein antibody mimics) will be created that can be used to select for binders to L-protein targets. By establishing chemical access to a number of D-proteins, their chemical properties can be tailored to maximize the desired biological response. These studies will provide a sound basis for the development of D-proteins as a modern class of intracellular protein therapeutics.