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• W1608385296 startingPage "1783" @default.
• W1608385296 abstract "Abstract L ‐Arginine hydrochloride ( L ‐ArgHCl) was found to be an effective enhancer for in vitro protein refolding more than two decades ago. A detailed understanding of the mechanism of action, by which L ‐ArgHCl as co‐solvent is capable to effectively suppress protein aggregation, while protein stability is preserved, has remained elusive. Concepts for the effects of co‐solvents, which have been established over the last decades, were found to be insufficient to completely explain the effects of L ‐ArgHCl on protein refolding. In this article, we present data, which clearly establish that L ‐ArgHCl acts on the equilibrium solubility of the native model protein recombinant plasminogen activator (rPA), while for S ‐carboxymethylated rPA (IAA‐rPA) that served as a model protein for denatured protein states, equilibrium solubilities could not be obtained. Solid to solute free transfer energies for native rPA were lowered by up to 14 kJ mol ‐1 under the tested conditions. This finding is in marked contrast to a previously proposed model in which L ‐ArgHCl acts as a neutral crowder which exclusively has an influence on the stability of the transition state of aggregation. The effects on the apparent solubility of IAA‐rPA, as well as on the aggregation kinetics of all studied protein species, that were observed in the present work could tentatively be explained within the framework of a nucleation‐aggregation scheme, in which L ‐ArgHCl exerts a strong effect on the pre‐equilibria leading to formation of the aggregation seed." @default.
• W1608385296 created "2016-06-24" @default.
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• W1608385296 date "2010-08-23" @default.
• W1608385296 modified "2023-10-07" @default.
• W1608385296 title "<scp>L</scp>-Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA" @default.
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• W1608385296 doi "https://doi.org/10.1002/pro.465" @default.
• W1608385296 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2975141" @default.
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