Serine-Selective Aerobic Cleavage of Peptides and a Protein Using a Water-Soluble Copper–Organoradical Conjugate†
Yohei Seki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Kana Tanabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Daisuke Sasaki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Youhei Sohma
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorCorresponding Author
Dr. Kounosuke Oisaki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)Search for more papers by this authorCorresponding Author
Prof. Dr. Motomu Kanai
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)Search for more papers by this authorYohei Seki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Kana Tanabe
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Daisuke Sasaki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorDr. Youhei Sohma
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Search for more papers by this authorCorresponding Author
Dr. Kounosuke Oisaki
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)Search for more papers by this authorCorresponding Author
Prof. Dr. Motomu Kanai
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
Japan Science and Technology Agency (JST), ERATO, Kanai Life Science Catalysis Project, Bunkyo-ku, Tokyo 113-0033 (Japan)
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)Search for more papers by this authorThis work was supported by a Grant in-Aid for Young Scientist B and Scientific Research C from JSPS (for K.O.), and ERATO from JST (for M.K.). We thank T. Sonobe, Dr. Y. Aoi, and Dr. S. Kawashima for fruitful discussions.
Graphical Abstract
Peptides and proteins can be cleaved selectively at serine residues under mild (room temperature, near neutral pH value) aerobic conditions by a water-soluble copper–organoradical conjugate. The method is applicable to the site-selective cleavage of polypeptides that possess various functional groups, D-amino acids, or sensitive disulfide pairs. The system was also used for the site-selective cleavage of a native protein comprising more than 70 amino acid residues.
Abstract
The site-specific cleavage of peptide bonds is an important chemical modification of biologically relevant macromolecules. The reaction is not only used for routine structural determination of peptides, but is also a potential artificial modulator of protein function. Realizing the substrate scope beyond the conventional chemical or enzymatic cleavage of peptide bonds is, however, a formidable challenge. Here we report a serine-selective peptide-cleavage protocol that proceeds at room temperature and near neutral pH value, through mild aerobic oxidation promoted by a water-soluble copper–organoradical conjugate. The method is applicable to the site-selective cleavage of polypeptides that possess various functional groups. Peptides comprising D-amino acids or sensitive disulfide pairs are competent substrates. The system is extendable to the site-selective cleavage of a native protein, ubiquitin, which comprises more than 70 amino acid residues.
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