An engineered human IgG1 CH2 domain with decreased aggregation and nonspecific binding.

ABSTRACT: The immunoglobulin (Ig) CH2 domain is a promising scaffold for the development of candidate therapeutics. We have previously shown that the stability of isolated CH2 could be increased by the introduction of an additional disulfide bond and removal of seven N-terminal residues (m01s). However, both isolated CH2 and m01s aggregate, likely due to the existence of aggregation-prone regions (APRs) that we identified by using computational methods. This knowledge was used to generate a phage display library of mutants. The library was incubated at high temperature to remove aggregating CH2 domains, and then panned against a mouse anti-human CH2 monoclonal antibody targeting a conformational epitope to remove misfolded CH2s. After two rounds of panning, one clone, m01s5, with smaller APRs, was i

SUBMITTER: Cao G 

PROVIDER: S-EPMC6927756 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature