H/D exchange links changes in conformational dynamics to decreased physical stability in an IgG1 mAb triple mutant with improved pharmacokinetic properties

摘要

The YTE mutation increases local flexibility in the 244-255 segment of the C_H2 domain resulting in decreased conformational stability. Increased flexibility of the Heavy Chain 244-255 segment has previously been correlated to decreased stability and increased aggregation in other IgG1 mAbs. [2, 3, 4, 5, 6].