2024/12/13
Keio University
Institute of Science Tokyo
A joint research group, including Lecturer Kengo Hanaya and Associate Professor Kazuaki Taguchi from the Faculty of Pharmacy, Keio University, and Professor Masanori Kono and Assistant Professor Yuki Wada from the Department of Chemistry, School of Science, Institute of Science Tokyo, has developed a simple chemical modification method for conjugating functional artificial molecules, such as fluorescent and pharmaceutical molecules, to the N-terminus of proteins using commercially available maleimide derivatives.
Chemical modification of proteins is a technique that adds new functions to proteins by conjugating artificial molecules to specific amino acid residues. This technology is utilized not only in life science research aimed at elucidating protein functions but also in a wide range of fields, including drug discovery. In particular, maleimide is known as a compound that specifically reacts with cysteine, a type of amino acid. Its derivatives, conjugated with various functional molecules, are commercially available and are one of the most widely used reagents in the chemical modification of proteins. However, many proteins do not have cysteine residues that can react with maleimide. Therefore, a challenge has been that the proteins amenable to chemical modification using maleimide derivatives are limited.
In this study, the research group overcame this challenge by developing a novel method for chemically modifying the N-terminal amino acid by adding 2-PCA and a copper(II) salt along with a maleimide derivative to the protein. This method does not require specific amino acid residues or sequences and is applicable to a wide range of proteins. Furthermore, they successfully created N-terminally cross-linked protein-protein complexes and antibody-drug conjugates (ADCs), significantly expanding the scope of chemical modification methods using maleimide derivatives.
This achievement opens up new possibilities for the development of protein-based biopharmaceuticals and biomaterials and is expected to contribute to various scientific fields. The results of this research were published in the international academic journal "Angewandte Chemie International Edition" on November 27, 2024.
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