Comprehensive elucidation of the structural and functional roles of engineered disulfide bonds in antibody Fc fragment.

ABSTRACT: Therapeutic monoclonal antibodies and Fc-fusion proteins containing antibody Fc fragment may tend to destabilize (e.g. unfold and aggregate), which leads to loss of functions and increase of adverse risks. Although engineering of an additional disulfide bond has been performed in Fc or Fc domains for optimization, the relationships between introduced disulfide bond and alteration of the stability, aggregation propensity and function were still unclear and should be addressed for achievement of better therapeutic outcome. Here, we constructed three human IgG1 Fc mutants including Fc^CH2-s-s- (one engineered disulfide bond in CH2 domain), Fc_CH3-s-s- (one engineered disulfide bond in CH3 domain), and Fc_CH3-s-s- ^CH2-s-s- (two engineered disulfi

SUBMITTER: Zeng F 

PROVIDER: S-EPMC6295723 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature