Alternative Setups for Automated Peptide Synthesis

Nowadays, lithographic methods facilitate the combinatorial synthesis of >50.000 oligonucleotides per cm2, an achievement that revolutionized the whole field of genomics. High-density peptide arrays might spark a similar development for the field of proteomics, but all lithographic methods have a peptide specific disadvantage that impairs their use for peptide synthesis: Each monomer must be coupled separately to the solid support. This adds up to an excessive number of coupling cycles, especially when comparing the 4 x 20 coupling cycles that would generate an array of 20meric oligonucleotides, to the 20 x 20 cycles that would yield an array of 20meric peptides. This review mainly discusses one recent development that leads to very high-density peptide arrays: the combinatorial chemical synthesis based on electrically charged solid amino acid particles. Either a colour laser printer or a chip addresses the different charged amino acid particles to a solid support, where the whole layer of solid amino acid particles is melted. Hitherto immobilized amino acids then start to diffuse to the support, where all the 20 different amino acids couple in a spatially defined manner, and in one single coupling reaction to the support. The method should allow for the translation of entire genomes into sets of overlapping peptides to be used in proteome research.