This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major goal of this project is to understand the chemical and physical aspects of chaperoned refolding of proteins with synthetic polymers. Bio-compatible polymer polyethylene glycol (PEG) can perform a chaperone function at concentrations wherein PEG:protein ratio is large enough to sterically prevent proteins to self associate. We hypothesize that the attachment of a hydrophobic block to the PEG segment would lead to a better targeting of the hydrophobic domains of unfolded proteins and, thus decrease the quantity of polymer required for preventing protein aggregation and enabling efficient refolding to concentrations well tolerated by the human body. We performed a series of SAXS experiments to determine the level at which several di-block and tri-block copolymer surfactants are able to prevent aggregation of thermally unfolded proteins. Questions we addressed were: How does the relative block size in a surfactant and its concentration influence the unfolding/refolding process? Is there an optimal surfactant concentration that effectively prevents aggregation? SAXS investigations demonstrated that non-ionic amphiphilic tri-block copolymers of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (poloxamers) are able to prevent the aggregation of unfolded proteins and enhance their refolding yield. Our data indicate that certain poloxamers are able to perform a chaperone function at stoichiometric concentrations significantly lower than that reported for PEG. These results might be significant for the development of therapies that reestablish tissue structure, function and viability after physical tra
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