Abstract
AbstractHuman alpha‐1‐antitrypsin (A1AT), a native serine‐protease inhibitor that protects tissue damage from excessive protease activities, is used as an augmentation therapy to treat A1AT‐deficienct patients. However, A1AT is sensitive to oxidation‐mediated deactivation and has a short circulating half‐life. Currently, there is no method that can effectively protect therapeutic proteins from oxidative damage in vivo. Here we developed a novel biocompatible selenopolypeptide and site‐specifically conjugated it with A1AT. The conjugated A1AT fully retained its inhibitory activity on neutrophil elastase, enhanced oxidation resistance, extended the serum half‐life, and afforded long‐lasting protective efficacy in a mouse model of acute lung injury. These results demonstrated that conjugating A1AT with the designed selenopolymer is a viable strategy to improve its pharmacological properties, which could potentially further be applied to a variety of oxidation sensitive biotherapeutics.
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