The emergence of chemical genetics has led to the isolation of small molecules that are able to alter biochemical processes. A recently developed technology, SICLOPPS, allows for the generation of plasmid libraries that encode for the production of random cyclic peptides in vivo. In this proposal, SICLOPPS technology will be coupled with a screen to isolate cyclic peptides that inhibit the function of a trimeric enzyme from the purine biosynthetic pathway (FGAM synthetase). Identified peptides will be purified, quantified, and tested in vitro to verify FGAM synthetase inhibition. Purified peptides will also be tested for the ability to inhibit culture growth when added exogenously. Completion of the project will result in the characterization of new chemical genetic tools and validate the usefulness of cyclic peptides as small molecule effectors. ? ?
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