Peptides play a significant role in the defense mechanisms of the body and binding of cells, bacteria and viruses to surfaces. Combinatorial peptide chemistry has emerged as a powerful tool for mapping receptor-ligand interactions in drug discovery applications as well as epitope mapping. There is a huge, but largely unrealized, potential for peptide microarray applications in drug discovery, study of cellular pathways and treatment of tumors. There are two reasons why the peptide micro arrays have not yet reached their potential: i) the enormous diversity possible with peptide microarrays as well as ii) the high cost of peptide microarrays in comparison to DNA microarrays. In this proposal our goals are to: 1) Develop a highly flexible and fast in situ custom peptide synthesis technology which can lower the cost of peptide microarrays by at least an order of magnitude and reduce the synthesis time to less than 24 hours for peptides containing up to 15 amino acids;2) Increase the density of peptides on a microarray by an order of magnitude to >10,000/array;3) Use fluorescent probes as well as high resolution mass spectroscopy to determine sequence purity and stepwise yields for addition of each of the 20 naturally occurring amino acids. We have developed a revolutionary light gated oligonucleotide microarray synthesis technology which uses off the shelf reagents and a modified projector to carry out custom microarray synthesis on open or curved surfaces with probe densities of up to 500K/glass slide for about one tenth the cost of most commercial microarrays of similar density. In this project we will modify the chemistry and instrumentation used for oligonucelotide microarray synthesis to develop a system for combinatorial peptide synthesis on open/closed slide surfaces or membranes.