Abstract
Nowadays, the development of research tools and pharmaceuticals utilizing various functions of antibodies is receiving much attention, and there is also an interest in IgG-binding peptides(IgBP) having an affinity to the Fc region of antibodies. Selective chemical modification at the Fc region that does not affect its antigen recognition is beneficial not only for improving the quality of the antibody-drug conjugate(ADC) but also for creating a new functional antibody. On the other hand, IgBP is also expected to be applied to the development of antibody-dependent DDS. In this review, we firstly introduce the development of IgBP-mediated non-covalent-type ADC. As a payload, plinabulin, an anticancer and vascular disrupting drug now in Phase III, created by our group, was used. The IgBP-Plinabulin conjugate showed a reasonable binding affinity to the antibody, Herceptin. And, Herceptin-dependent cytotoxic effect of Plinabulin, via the cell internalization of noncovalent Herceptin-Plinabulin complex, was proved in vitro cell evaluation. Secondly, we introduce the development of a new small monocyclic IgBP(Lys8Leu/His17(2-Pya)-OH) with the strongest affinity(Kd = 2.48 nM) and slow-releasing property to the Fc region of IgG based on the structure-activity relationship study from a 17-residue IgBP 2 discovered by the phage-display screening. This potent IgBP would become a promising tag for antibody-dependent DDS in future.
