Nonspecific shielding of unfavorable electrostatic intramolecular interactions in the erythropoietin native-state increase conformational stability and limit non-native aggregation.

ABSTRACT: Previous equilibrium and kinetic folding studies of the glycoprotein erythropoietin indicate that sodium chloride increases the conformational stability of this therapeutically important cytokine, ostensibly by stabilizing the native-state [Banks DD, (2011) The Effect of Glycosylation on the Folding Kinetics of Erythropoietin. J Mol Biol 412:536-550]. The focus of the current report is to determine the underlying cause of the salt dependent increase in erythropoietin conformational stability and to understand if it has any impact on aggregation, an instability that remains a challenge to the biotech industry in maintaining the efficacy and shelf-life of protein therapeutics. Isothermal urea denaturation experiments conducted at numerous temperatures in the absence and presence of sodium ch

SUBMITTER: Banks DD 

PROVIDER: S-EPMC4420528 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature