Preparation and Biological Activity of PEGylated DesB30 Human Insulin

Detemir that a 14-C fatty acid chain is attached to position B29 of DesB30 human insulin is a soluble insulin analog developed to ensure appropriate basal insulin supply. PEGylation is one way to prolong the time of insulin action. In this study methyl polyethylene glycol succinimidyl propionate (mPEG-SPA )was used as substitutes for 14-C fatty acid to modify the DesB30 human insulin. We will show in this manuscript that it is possible to identify mPEG-SPA modified insulin analogs with steady metabolic activity and longer duration of action than Detemir. The modification products of DesB30 human insulin (HIDesB30): HIDesB30-PEG1, HIDesB30-PEG2, and HIDesB30-PEG3 were obtained. Diabetes was induced in mice using streptozotocin (STZ). The duration of action of HIDesB30-PEG2 was more than 36 hours, and the metabolic activity was constant over the study period. HIDesB30-PEG2 could be a potential novel long acting human insulin analog for the treatment of diabetes.