Homology modeling and structure-based design improve hydrophobic interaction chromatography behavior of integrin binding antibodies.

ABSTRACT: Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack of solubility. In this work, we optimized a candidate integrin α11-binding mAb for developability using molecular modeling, rational design, and hydrophobic interaction chromatography (HIC). A homology model of the parental mAb Fv region was built, and this revealed hydrophobic patches on the surface of the complementarity-determining region loops. A series of 97 variants of the residues primarily responsible for the hydrophobic patches were expressed and their HIC retention times (RT) were measured. As intended, many of the computationally designed variants red

SUBMITTER: Jetha A 

PROVIDER: S-EPMC6152428 | biostudies-literature | 2018 Aug/Sep

REPOSITORIES: biostudies-literature