Peptide synthesis photolithographic

A special case of parallel synthesis is the spatially addressable synthesis pioneered by Fodor et al. [17,18] in 1991. Here, each member of the library is synthesized at a specific location on a functionalized silica wafer rather than on resin beads in separate reaction vessels. This approach, based initially upon solid-phase peptide synthesis and semiconductor photolithographic techniques by using photolabile amino protecting groups, allows the synthesis of combinatorial libraries containing about 50000 compounds localized to a 50 pm square site on a silica wafer ( library on a chip ). 

Oligonucleotide and peptide microarrays can be prepared in situ with light-directed synthesis on a glass surface in conjunction with either a photolithographic method or using a micromirror device (2,11-15). However, these methods are not useful for most organic synthesis. Furthermore, such approaches require equipment that is not readily available. Spot synthesis on cellulose membrane is another in situ synthesis method, but the resulting microarrays are low density (16). 

Chemical diversity for chemical microarrays can be accessed in two ways importing compounds onto the chip surface or synthetically creating molecules directly on the support. In the pioneering work by Fodor and coworkers, a combination of solid-phase organic synthesis and photolithographic techniques was applied to the in siiu creation of oligonucleotide and peptide microarrays [54, 55]. 

With the same number of chemical steps, the diversity and number of peptides synthesized using light-directed, spatially addressable chemical synthesis depends, among other factors, on the patterns of photolithographic masks used for each photodeprotection. Different masking strategies can be used. 

Li S, Marthandan N, Bowerman D, Garner HR, Kodadek T (2005) Photolithographic synthesis of cyclic peptide arrays using a differential deprotection strategy. Chem Comm pp 581-583... 

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