Synthesis and Folding of Seleno-Insulin

Insulin has been the premier drug for improving the quality of life for diabetes mellitus patients. Since the early 1960s, chain A and chain B of insulin were successfully synthesized; however the recombination of these chains to form mature native insulin remains ineffective due to the numerous non-native disulfide links, and peptide precipitation. Many research groups have showed total chemical synthesis of fully active insulin, or analogs that show higher stability. Our Research project proposes an alternative approach for the preparation of human insulin analogs by substitution of pair of cysteine residues by selenocysteine, the 21st encoded amino acid. Since it has been shown that selenium enhances the oxidative folding and diselenide bonds are more stable that disulfide bonds, we expect to obtain an improvement of stability and recombination of the chains in higher yields. Here we show the different results obtained with our Selenoinsulin in comparison to the human insulin wt.