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Microwave technology for solid phase peptide synthesis – It’s not just for difficult peptides


*Corresponding author
CEM Corporation Life Science Division, P.O. Box 200 Matthews, NC 28106, USA


The use of microwave technology for solid phase peptide synthesis is one of the most significant breakthroughs of the past decade in the field of peptide chemistry. Much of the research on microwave-assisted peptide synthesis has focused on difficult to synthesize peptides. Described herein is an extensive study of the standard microwave synthesis protocols for the synthesis of a series of peptides that span a range of complexities. Each peptide was rapidly prepared in excellent purity, and often the microwave method far outperformed conventional synthesis techniques.


Microwave technology is quickly becoming the preferred tool for performing solid phase peptide synthesis, especially for the synthesis of “difficult” peptides (1-4). Microwave irradiation significantly reduces the synthesis time while also improving the quality of the peptides produced. Routine methods have been developed that minimize the potential for side reactions including the racemization of the cysteine and histidine residues during coupling and aspartimide formation in aspartic acid containing sequences during Fmoc deprotection (5).
While nearly 100 papers are published annually that highlight the use of microwave technology for performing peptide synthesis, many of these studies focus on the synthesis of “difficult” peptides (6-12). The use of microwave energy to promote peptide synthesis provides two advantages over conventional room temperature synthesis conditions: significantly faster reaction times and in many cases higher purity peptide product. During the peptide synthesis process there are many polar and ionic species present that can be rapidly heated by microwave energy. The resulting temperature increase c ...

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