Advantage and Core Benefit

・Natural proteins are easily functionalized.
・Homogeneous proteins site-specifically liked with a molecule are obtained without any reaction on sidechain.
・No limitation of N-terminal amino acid residue.

＜Potential Applications＞
・Pharmaceuticals: Antibody-drug conjugates (ADCs), PEGylation, New modalities (e.g. DNA aptamer-antibody Fc conjugates), TR-FRET libraries for drug discovery, Radio-active labeling for pharmacokinetics
・Diagnostics: ELISA/RIA, PET/SPECT

Background and Technology

There are several protein linking methods for functionalization. Some methods non-specifically modify functional groups of protein, which might affect original function of the protein, whereas others need protein modification at a gene design level.
Newly developed linker 1H-1,2,3-triazole-4-carbaldehyde (TA4C) derivatives selectively react with N-terminal amine of proteins, which enable to efficiently introduce new functional groups without modifying original function/structure of protein (fig.L).

Data

・TA4C-payloads are easily synthesized with 1-3 steps using previously reported methods.
・Half-life can be controlled from several hours to one week.
・Fluorescent dye-conjugated trastuzumab shows the same affinity as the original one and fluoresced on the Her2 expressing cell surface (fig.R).

Expectations

・We are seeking companies to license and commercialize this technology.
・Samples for your evaluation are available under material transfer agreement (MTA).

Principal Investigator

Prof. Akira Onoda (Hokkaido University)

Patents and Publications

Patents
PCT/JP2020/008357; US, EP, CN, JP

Publications
https://doi.org/10.1002/cbic.201900692