Intein-mediated backbone cyclization of entolimod confers enhanced radioprotective activity in mouse models.

ABSTRACT:

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

SUBMITTER: Ye B 

PROVIDER: S-EPMC6011820 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature