Development of a high affinity, non-covalent biologic to add functionality to Fabs.

ABSTRACT: Functionalization of monoclonal antibodies (mAbs) requires chemical derivatization and/or genetic manipulation. Inherent in these methods are challenges with protein heterogeneity, stability and solubility. Such perturbations could potentially be avoided by using a high affinity, non-covalent intermediate to bridge the desired functionality to a stable mAb. Recently, we engineered a binding site for a peptide named "meditope" within the Fab of trastuzumab. Proximity of the meditope site to that of protein L suggested an opportunity to enhance the meditope's moderate affinity. Joined by a peptide linker, the meditope-protein L construct has a KD ~ 180 pM - a 7000-fold increase in affinity. The construct is highly specific to the engineered trastuzumab, as demonstrated by flow cytometry. Mor

SUBMITTER: Avery KN 

PROVIDER: S-EPMC4295097 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature