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Publication Abstract from PubMed

Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7UA ,C7UB ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (tau1/2 approximately 8 h vs. approximately 1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.

Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue.,Arai K, Takei T, Okumura M, Watanabe S, Amagai Y, Asahina Y, Moroder L, Hojo H, Inaba K, Iwaoka M Angew Chem Int Ed Engl. 2017 May 8;56(20):5522-5526. doi: 10.1002/anie.201701654., Epub 2017 Apr 10. PMID:28394477^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.