Serine-selective aerobic cleavage of peptides and a protein using a water-soluble copper-organoradical conjugate.
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.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Yohei
Y
Seki
Kana
K
Tanabe
Daisuke
D
Sasaki
Youhei
Y
Sohma
Kounosuke
K
Oisaki
Motomu
M
Kanai
D000595:Amino Acid Sequence; D003300:Copper / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012694:Serine / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*
D010455:Peptides; D011506:Proteins; D014867:Water; D012694:Serine; D003300:Copper; D010100:Oxygen
aerobic oxidation; copper; peptide bonds; proteins; serine