Biomacromolecules p. 3086 - 3095 (2018)
Update date:2022-08-11
Topics:
Chou, Chih-Hung
Lin, Po-Chiao
Antibody and related antibody drugs for the treatment of malignancies have led to progress in targeted cancer therapy. Preparation of diverse antibody conjugates is critical for preclinical and clinical applications. However, precise control in tagging molecules at specific locations on antibodies is essential to preserve their native function. In this study, a synthetic boronic acid (BA)-tosyl initiator was used to trigger a glycan-directed modification of IgGs, and the obtained IgG macroinitiators allowed a growth of the poly N-isopropylacrylamide (PNIPAAm) chains specifically at Fc-domains. Therefore, the PNIPAAm chains are located away from the critical antigen-binding domains (Fab), which could reasonably prevent the loss of biological activity after the attachment of polymer chains. According to the proposed strategy, a site-selectively modified anticoncanavalin A (Con A) antibody-PNIPAAm conjugate showed 6-times higher efficiency in the binding of targeted Con A antigen to a randomly conjugated anti-Con A antibody-PNIPAAm conjugate. In this study, we developed the first chemical strategy for the site-specific preparation of IgG-polymer conjugates with conserved biological activity as well as intact glycan structures.
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Doi:10.1002/cctc.202001411
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