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Updated: Jun 5, 2026

Surface Passivation for Single-molecule Protein Studies
Published on: April 24, 2014
The effect of PEGylation on the stability of small therapeutic proteins
Thomas Palm1, Reza Esfandiary, Rajesh Gandhi
1Bristol-Myers Squibb, Biopharmaceutics R&D, New Brunswick, PO Box 191, New Jersey 08903-0191, USA. Thomas.Palm@bms.com
Abstract:
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.
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