The Development of Multimeric Bioscavenger Complexes
Abstract
To enhance the circulatory stability of candidate organophosphorus nerve agent bioscavenger enzymes, we aimed to develop an approach based on the assumption that increasing the molecular weight (MW) of smaller proteins could prolong in vivo retention. Our goal was to create a new type of complex with an avidin core with the ability to support up to four bioscavengers, increasing the overall size while maintaining access to enzyme sites. This approach is in contrast to multimeric bioscavenger-containing liposomes and nanoparticles, where the protein is not necessarily accessible until it is released. Our strategy requires biotinylation of the bioscavenger, followed by multimeric crosslinking mediated by a compound such as streptavidin, which can bind to multiple biotin molecules. In summary, we generated an enzymatically active PON1 variant that can be specifically biotinylated at a single site, completing the first steps to allow controlled assembly of multimeric bioscavenger complexes containing between one and four different bioscavenger proteins per complex.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2018
- Accession Number
- AD1057860
Entities
People
- Bryan J. Mccranor
- Deborah Moorad-doctor
- Gregory E. Garcia
- Melissa A. Olert
- Nazira A. Alli
Organizations
- United States Army Medical Research Institute of Chemical Defense