Chemical Synthesis of Insulins

by Michael Pennington

The members from the lab of Richard DiMarchi have recently published a very comprehensive review ( about the chemical synthesis of peptides from the insulin super family. As everyone knows, insulin peptides represent some of the toughest molecules to synthesize due to the presence of both intra- and intermolecular disulfide bonds linking the A and B chains. Additionally, syntheses of the two chains are not trivial, nor is their reconstitution in the appropriate oxidative folding buffers. In this review, Liu, et al., present a historical overview of the chemical methods developed in the early 1960’s up to the present culminating with their improved strategies for making insulin in one pot as well as coverage of synthesis of insulin like peptides such as IGF-II and relaxin. For those of us interested in disulfide rich peptides, this is an excellent review especially for making these bonds sequentially.

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