Abstract
The application of microwave irradiation to solid-phase peptide synthesis increases product purity and reduces reaction time. Parallel synthesis in 96-well polypropylene filter plates with microwave irradiation is an efficient method for the rapid generation of combinatorial peptide libraries in sufficient purity to assay the products directly for biological activity without HPLC purification. In this protocol, the solid-phase support is arrayed into each well of a 96-well plate, reagents are delivered using a multichannel pipette and a microwave reactor is used to complete peptide coupling reactions in 6 min and Fmoc-removal reactions in 4 min under temperature-controlled conditions. The microwave-assisted parallel peptide synthesis protocol has been used to generate a library of difficult hexa-β-peptides in 61% average initial purity (50% yield) and has been applied to the preparation of longer α- and β-peptides. Using this protocol, a library of 96 different hexapeptides can be synthesized in 24 h (excluding characterization).
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Change history
31 May 2007
In the version of this article originally published online, Justin Murray’s affiliation was shown as Amgen, but at the time the work was done he was at the University of Wisconsin–Madison. This error has been corrected in the PDF version of the article.
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Murray, J., Gellman, S. Parallel synthesis of peptide libraries using microwave irradiation. Nat Protoc 2, 624–631 (2007). https://doi.org/10.1038/nprot.2007.23
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DOI: https://doi.org/10.1038/nprot.2007.23
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