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Isoacyl dipeptides to increase insulin yield from chemical synthesis

Chemical synthesis of insulin using isoacyl dipeptides could improve yield of the hormone. Synthesis of insulin-a protein composed of two peptide chains-is inefficient, with yields generally less than 15%. Incorporation of an isoacyl dipeptide into the insulin A chain improved purification of the peptide and enabled on-resin intramolecular disulfide bond formation. Incorporation of an isoacyl dipeptide in the insulin B chain increased yield compared with no isoacyl dipeptide. Subsequent ligation of the two chains produced insulin with an overall yield of 24%. Next steps could include further optimizing the synthesis process.

SciBX 7(15); doi:10.1038/scibx.2014.440
Published online April 17, 2014

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Liu, F. et al. Angew. Chem. Int. Ed.; published online March 11, 2014;
Contact: Fa Liu, Eli Lilly & Co., Indianapolis, Ind.