Autor: |
Bingyu Ye, Wenlong Shen, Minglei Shi, Yan Zhang, Cunshuan Xu, Zhihu Zhao |
Jazyk: |
angličtina |
Rok vydání: |
2018 |
Předmět: |
|
Zdroj: |
PeerJ, Vol 6, p e5043 (2018) |
Druh dokumentu: |
article |
ISSN: |
2167-8359 |
DOI: |
10.7717/peerj.5043 |
Popis: |
Background Entolimod is a Salmonella enterica flagellin derivate. Previous work has demonstrated that entolimod effectively protects mice and non-human primates from ionizing radiation. However, it caused a “flu-like” syndrome after radioprotective and anticancer clinical application, indicating some type of immunogenicity and toxicity. Cyclization is commonly used to improve the in vivo stability and activity of peptides and proteins. Methods We designed and constructed cyclic entolimod using split Nostoc punctiforme DnaE intein with almost 100% cyclization efficiency. We adopted different strategies to purify the linear and circular entolimod due to their different topologies. Both of linear and circular entolimod were first purified by Ni-chelating affinity chromatography, and then the linear and circular entolimod were purified by size-exclusion and ion-exchange chromatography, respectively. Results The circular entolimod showed significantly increased both the in vitro NF-κB signaling and in vivo radioprotective activity in mice. Conclusion Our data indicates that circular entolimod might be a good candidate for further clinical investigation. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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