Novel Selective Methionine Bioconjugation Method Developed

ON2017-02-17TAG: 上海科技大学CATEGORY: Published Research


Post-translational modification (PTM) plays an important role in regulating the physiological activity of proteins, controlling the enzyme catalytic activity and protein-protein recognition in the biological process. The chemical modification of proteins can study the physiological mechanism of proteins by mimic PTM process, as well as tracking proteins in vitro/vivo and developing therapeutic protein conjugates, particularly antibody drug conjugates. Recently, Dr. Xiaoyu Yang, an assistant professor of materials biology research department at School of Physical Science and Technology (SPST), and his collaborators, have made a breakthrough in selective methionine bioconjugation, which was published in the journal of Science on Feb. 10th, titled “Redox-based reagents for chemoselective methionine bioconjugation”. The study was conducted by Professor Christopher J. Chang and Professor F. Dean Toste, Department of Chemistry, University of California Berkeley. Dr. Xiaoyu Yang is the co-first author of the paper and ShanghaiTech University is one of the affiliations.

Dr. Xiaoyu Yang and his collaborators developed a novel chemical labeling strategy, termed Redox Activated Chemical Tagging (ReACT), which for the first time enables chemoselective methionine bioconjugation in proteins and proteomes. In their work, they reported using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions. Dr Xiaoyu Yang and co-workers also highlighted the broad utility of this conjugation method to enable precise addition of payloads to proteins, synthesis of antibody-drug conjugates, and identification of hyper-reactive methionine residues in whole proteomes.

This breakthrough protein bioconjugation technology has great potential in the field of life science research and biomedicine development. In life science study, it can mimic the post-translational modification (PTM) in nature, which is used to study the mechanism of protein physiological function. In the field of biomedicine development, it can be used to develop therapeutic protein conjugates, especially antibody drug conjugates (ADCs). Antibody drug conjugates (ADCs) are a new class of therapeutic agents, gaining increasing attention from pharmaceutical companies. ADCs are constituted by monoclonal antibodies and potent toxic drugs through the biologically active linker, serving as efficient targeted anti-cancer drugs. Because of its accurate identification of targeted and non-cancer cells, it can greatly reduce the toxic side effects and improve efficacy. A report released by Research & Markets, a well-known global market research company in 2014, shows that the ADC market will experience rapid growth over the next 10 years and is expected to reach $ 10 billion in 2024.ows that the ADC market will experience rapid growth over the next 10 years and is expected to reach $ 10 billion in 2024.

Article Link: http://science.sciencemag.org/content/355/6325/597

News Link: http://cen.acs.org/articles/95/i7/Modifying-methionine-proteins.html