The effect of PEGylation on the stability of small therapeutic proteins.
The influence of PEGylation on the thermal stability of small therapeutic proteins was evaluated using two model proteins. Changes in the midpoint of thermal unfolding and the ability to properly refold after thermal denaturation were monitored by differential scanning calorimetry (DSC) as a function of PEGylation and pH. The results showed that PEGylation increased the thermal stability of both model proteins as well as their ability to refold properly after thermal denaturation. The DSC results were compared to traditional accelerated stability data that were collected using size exclusion high performance liquid chromatography (SE-HPLC). The DSC data agreed reasonably well with those from SE-HPLC indicating that microcalorimetry can be an efficient screening tool for PEGylated proteins.
Bristol-Myers Squibb, Biopharmaceutics R&D, New Brunswick, PO Box 191, New Jersey 08903-0191, USA. Thomas.Palm@bms.com
Thomas
T
Palm
Reza
R
Esfandiary
Rajesh
R
Gandhi
D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011489:Protein Denaturation; D017510:Protein Folding; D055550:Protein Stability; D013696:Temperature
C549678:CT-322; D005353:Fibronectins; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D011092:Polyethylene Glycols