Predicting deamidation and isomerization sites in therapeutic antibodies using structure-based in silico approaches.

ABSTRACT: Asparagine (Asn) deamidation and aspartic acid (Asp) isomerization are common degradation pathways that affect the stability of therapeutic antibodies. These modifications can pose a significant challenge in the development of biopharmaceuticals. As such, the early engineering and selection of chemically stable monoclonal antibodies (mAbs) can substantially mitigate the risk of subsequent failure. In this study, we introduce a novel in silico approach for predicting deamidation and isomerization sites in therapeutic antibodies by analyzing the structural environment surrounding asparagine and aspartate residues. The resulting quantitative structure-activity relationship (QSAR) model was trained using previously published forced degradation data from 57 clinical-stage mAbs. The predictive a

SUBMITTER: Hoffmann D 

PROVIDER: S-EPMC10984128 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature