9410847 Brent This award is to facilitate an attemp to develop a method for selection of peptides which bind to a given target protein. The method involves displaying a collection of random, 20 amino acid peptides as part of a fusion protein with thioredoxin. The peptides are inserted into an internal region of this protein such that they presumably will be displayed on the surface of the protein in a conformation determined by their amino acid sequence and fixed by the tether to the protein. This library will then be sampled by the two-hybrid screening technique in S. cerevisiae. An appropriate "bait" construct will serve as a target for binding by one or more of the library members. The goal is to develop a general method for identifying peptide ligands to specific proteins. If successful, the method will have broad applications as a potential mechanism for in vivo inhibition of the activity of any target protein. %%% The award will be used to test the possibility that a system using protein-protein interactions in yeast can be applied to the identification of random, synthetic peptides that can bind to a specific target protein in any cell type. If the system works, it will be possible to identify peptides from a large, random collection which have very specific properties. Peptides with specific binding properties have an extremely broad range of potential application in regulating the activities of their targets inside living cells. These properties will be useful to biochemists studying mechanisms and properties of important proteins. Further, the potential to apply the method for the development of clinically useful anti-viral and anti-bacterial agents has not escaped our notice. ***
