Project Summary The requested instrument is a CEM microwave-assisted peptide synthesizer, the Liberty Prime 2.0 HT12 System, which builds up chemical libraries of peptidomimetics and produces small-size enzymes possessing >100 amino acids. With the aid of microwave heating system, the synthesizer features a short reaction time alongside a significant reduction of solvent usage and produces the desired products with high yield and purity for long and complex peptides. In addition, the engineered fluidic deliveries, internal temperature control, resin- transfer module, and software enhance throughput of synthesis, allowing up to 12 peptides to be queued at a time. The long-term objective of this application is to develop novel peptidomimetics and macrocyclic hybrids as therapeutic candidates for human diseases. We will also develop new classes of peptide-based biosensors of kinase to understand the functional biology of each kinase in living cells using the peptide synthesizer. We propose to acquire this instrument to synthesize peptidomimetics, peptide-sensors, and small enzymes efficiently in a cost-effective, eco-friendly, and educational manner. Our research projects use the traditional method of solid phase synthesis: using fritted plastic syringes and shakers. However, since the traditional method has long reaction times (2-3 hours per coupling step) and large amounts of solvents in the washing steps, progress in producing chemical libraries for the discovery of bioactive agents are currently limited. In addition, synthesizing long peptide chains with >10 amino acids results in inseparable mixtures and inconsistent results for many synthesized peptides. Thus, using the automated system will definitely elevate the productivity and consistency in our research projects. Since the system uses the significantly reduced solvents, it is also ideal for a resource-limited institution for research. Solid phase synthesis of peptides is an appropriate experiment to teach beginners in the lab, and new students are able to learn basic laboratory skills for their research with minimal training and by following protocols. In addition, students will learn amide coupling and deprotection reactions and instrumentation for analysis, purification, and characterization of peptides they synthesized. However, the traditional method requires excessive time and effort on tedious and repetitive steps such as washing resins with solvents, which tend to make students more engaged in making chemical agents rather than understanding their biological effects and learning rationale for improving their activities. Therefore, the automated peptide synthesizer can be an exemplary instrument to train entry level researchers such as high school and undergraduate students, and they will learn not only synthesis of peptidomimetics, but also their applications in therapeutic discovery and biomedical research.