AsianScientist (Aug. 18, 2017) – A group of researchers in Japan has succeeded in developing synthetic insulin analogs with long-lasting activity by replacing sulfur with selenium in the insulin sub-chains. They publish their results in the journal Angewandte Chemie International Edition.
Diabetes is caused by a defect in insulin signaling resulting in the body’s inability to control blood sugar levels. As a result, diabetics have to consistently monitor their blood glucose concentration, alter their diet and lifestyles, and administer insulin injections to regulate the amount of free sugar in their blood.
In this study, a group of researchers led by Dr. Kenta Arai and Professor Michio Iwaoka from Tokai University, Assistant Professor Masaki Okumura, Assistant Professor Satoshi Watanabe and Professor Kenji Inaba from Tohoku University, and Associate Professor Hojo Hironobu from Osaka University succeeded in developing synthetic insulin analogs selenoinsulin (Se-Ins) through the replacement of the interchain disulfide in bovine pancreatic insulin (BPIns) with a diselenide bridge.
Insulin consists of two polypeptide chains: A chain and B chain, connected by a disulfide bond between two sulfur (S) atoms. The group hypothesized that if insulin A-chains and B-chains contained selenium (Se) instead of sulfur, the diselenide bond (Se−Se bond) would be formed quickly and the chain-assembly reaction could be carried out efficiently, as Se is more reactive than S.
In addition, Se-Se bonds are more stable than S-S bonds, suggesting that Se-Se bonds would give extra structural robustness to the insulin fold, thus resulting in the enhanced resistance to Insulin Degrading Enzyme (IDE). Based on this concept, the researchers synthesized Se-containing insulin A and B chains and obtained Se-Ins at an isolation yield of up to 27 percent by reacting peptide chains under optimal conditions.
They subsequently demonstrated that Se-Ins had a nearly identical structure to that of BPIns, suggesting that Se-Ins has a bioactivity comparable to that of BPIns. Experiments on the degradation of BPIns and Se-Ins by IDE showed that the degradation rate of Se-Ins was much slower than that of BPIns. Hence, the researchers proposed that that Se-Ins has a long-lasting nature and could be a new class of long-acting insulin analogs for diabetes therapy.
The article can be found at: Arai et al. (2017) Preparation of Selenoinsulin as a Long-Lasting Insulin Analog.
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Source: Osaka University; Photo: Shutterstock.
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