Stability of Human Growth Hormone: Influence of Methionine Oxidation on Thermal Folding

Selective Domain Stabilization as a Strategy to Reduce Fusion Protein Aggregation

“…24 HSA-hGH fusion proteins were created with the goal of increasing the circulation half-life of hGH. 25 Although HSA aggregates more slowly than hGH at both pH 5 and 7, addition of the HSA domain to hGH does not result in improved kinetic stability of the therapeutic molecule against aggregation.…”

Engineering protein thermostability using a generic activity-independent biophysical screen inside the cell

“…More efficient strategies of stabilizing proteins could potentially reduce efforts in protein manufacturing and formulation, as well as improve the safety of protein drugs. Biopharmaceuticals that have reached the clinic are generally highly thermostable [1][2][3][4] . In contrast, many protein drug candidates in development are suffering from poor stability 5,6 , which will affect efficacy and can lead to increased immunogenicity of the biopharmaceutical, inhibiting their advancement to the clinic.…”

Forced Degradation of Therapeutic Proteins

“…0.003%) H 2 O 2 for recombinant human interleukin‐1 receptor56 or by 0.005% (v/v) H 2 O 2 for recombinant human interferon α‐2b 145. By applying mild oxidation conditions (H 2 O 2 at a molar ratio of 80:1 (H 2 O 2 :protein) for 4 h at 20°C) to recombinant human growth hormone, site‐specific oxidation of the relatively accessible Met14 and Met125 residues under preservation of the native conformation has been achieved 146,147. Not only the H 2 O 2 concentration but also the solution pH can influence the degree of oxidation, because normally buried Met residues can become accessible due to pH‐induced conformational changes, as shown for human α‐1 antitrypsin 148.…”