This proposal is directed towards the design, creation, and optimization of a fully automated peptide synthesis instrument capable of making over 100 peptides at a time using the broadly accepted FMOC chemistry in a parallel mode. This parallel approach will result in cycle times of less than 25 minutes for the simultaneous addition of 16 amino acids to up to 16 synthesis stacks each comprised of 1 to 8 synthesis wafers. Each wafer will produce up to a 20 micromole synthesis. Each peptide can be of completely independent sequence. Reagent consumption will be reduced by 50% over single synthesis instruments. Synthesis cost will be less than $2 per amino acid and enable the production of peptide libraries for applications requiring hundreds of peptides. Phase II will fully automate the Phase I synthesizer with an integral synthesis wafer sorter and the software to drive the operation of the machine and integrate it into a LIMS based peptide production facility. Another major goal is automation of post-synthesis processing to eliminate bottlenecks in the equally important phase of peptide production. Rapid and economical availability of hundreds of peptides will significantly accelerate research into biological activity screening, mutagenesis, structural studies, etc.
Final implementation of this technology will provide a machine for hundreds of peptide variations per day to enable studies of protein folding, site specific mutagenesis, hormone variant testing, antibody idiotype exploration, etc., while using considerably less reagents. The availability of multiple peptides empowers investigations that would take months just to synthesize the requisite peptides. All university core facilities, pharmaceutical companies and other large research institutions will benefit from the throughput of this synthesizer.
