L -Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA

摘要: 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 action, by which l-ArgHCl as co-solvent is capable effectively suppress aggregation, while stability preserved, has remained elusive. Concepts effects co-solvents, have been established over last decades, were insufficient completely explain on refolding. In this article, we present data, clearly establish that acts equilibrium solubility native model recombinant plasminogen activator (rPA), S-carboxymethylated rPA (IAA-rPA) served a denatured states, solubilities could not obtained. Solid solute free transfer energies lowered up 14 kJ mol-1 under tested conditions. This finding marked contrast previously proposed neutral crowder exclusively influence transition state aggregation. The apparent IAA-rPA, well aggregation kinetics all studied species, observed work tentatively explained within framework nucleation-aggregation scheme, exerts strong effect pre-equilibria leading formation seed.