title: Directed N-terminal elongation of unprotected peptides catalyzed by cathepsin C in water.
abstract: N-terminal chain extension of unprotected amino acid amides and peptides with dipeptide amides using Cathepsin C (dipeptidyl aminopeptidase I, EC 3.4.14.1)-mediated reverse proteolysis in water was studied. Taking Pro-X-NH2 as the acyl donor, the sensitivity of the kinetically controlled peptide, coupling to pH value, temperature, acetonitrile addition, and nucleophile type were investigated. Basic or hydrophobic amino acids as the alpha-amino-N-nucleophile proved to be much more prone to catalyzed bond formation than their neutral, hydrophilic, or negatively charged analogues. In a preparative run a pentapeptide was obtained with 83% yield by directed and regioselective coupling of ProTrpNH2 with LysLeuPheNH2 catalyzed by Cathepsin C in aqueous buffer.
authors.affiliation: Lehrstuhl für Organische Chemie und Biochemie, Technische Universität München, Garching, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Gittel
authors.forename: F P
authors.initials: FP
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D020789:Cathepsin C; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry* / Q000493:pharmacokinetics; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D010455:Peptides; D014867:Water; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C