Serine‐Selective Aerobic Cleavage of Peptides and a Protein Using a Water‐Soluble Copper–Organoradical Conjugate. (14th May 2014)

• Record Type: Journal Article
• Authors: Seki, Yohei; Tanabe, Kana; Sasaki, Daisuke; Sohma, Youhei; Oisaki, Kounosuke; Kanai, Motomu
• Is Part Of: Angewandte Chemie. Volume 126:Number 25(2014)
• Page Start: 6619
• Page End: 6623
• Publication Date: 2014-05-14
• Subjects: Aerobe Oxidation -- Kupfer -- Peptidbindungen -- Proteine -- Serin; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201402618
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Peptide und Proteine können unter milden (Raumtemperatur, annähernd neutraler pH), aeroben Bedingungen durch ein wasserlösliches Kupfer‐Organoradikal‐Konjugat selektiv an Serinresten gespalten werden. Die Methode ist anwendbar auf die ortsspezifische Spaltung von Polypeptiden mit verschiedenen funktionellen Gruppen, D ‐Aminosäuren oder empfindlichen Disulfidpaaren. Das System wurde außerdem für die ortsspezifische Spaltung eines natürlichen, aus über 70 Aminosäuren bestehenden Proteins verwendet.