Physicochemical Rules for Identifying Monoclonal Antibodies with Drug-like Specificity.

ABSTRACT: The ability of antibodies to recognize their target antigens with high specificity is fundamental to their natural function. Nevertheless, therapeutic antibodies display variable and difficult-to-predict levels of nonspecific and self-interactions that can lead to various drug development challenges, including antibody aggregation, abnormally high viscosity, and rapid antibody clearance. Here we report a method for predicting the overall specificity of antibodies in terms of their relative risk for displaying high levels of nonspecific or self-interactions at physiological conditions. We find that individual and combined sets of chemical rules that limit the maximum and minimum numbers of certain solvent-exposed amino acids in antibody variable regions are strong predictors of specificity

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC7936472 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature