Engineering an anti-CD52 antibody for enhanced deamidation stability.

ABSTRACT: Deamidation evaluation and mitigation is an important aspect of therapeutic antibody developability assessment. We investigated the structure and function of the Asn-Gly deamidation in a human anti-CD52 IgG1 antibody light chain complementarity-determining region 1, and risk mitigation through protein engineering. Antigen binding affinity was found to decrease about 400-fold when Asn³³ was replaced with an Asp residue to mimic the deamidation product, suggesting significant impacts on antibody function. Other variants made at Asn³³ (N33H, N33Q, N33H, N33R) were also found to result in significant loss of antigen binding affinity. The co-crystal structure of the antigen-binding fragment bound to a CD52 peptide mimetic was solved at 2.2Å (PDB code 6OBD), which revealed

SUBMITTER: Qiu H 

PROVIDER: S-EPMC6748592 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature