title: N-terminal modification of proteins with o-aminophenols.
abstract: The synthetic modification of proteins plays an important role in chemical biology and biomaterials science. These fields provide a constant need for chemical tools that can introduce new functionality in specific locations on protein surfaces. In this work, an oxidative strategy is demonstrated for the efficient modification of N-terminal residues on peptides and N-terminal proline residues on proteins. The strategy uses o-aminophenols or o-catechols that are oxidized to active coupling species in situ using potassium ferricyanide. Peptide screening results have revealed that many N-terminal amino acids can participate in this reaction, and that proline residues are particularly reactive. When applied to protein substrates, the reaction shows a stronger requirement for the proline group. Key advantages of the reaction include its fast second-order kinetics and ability to achieve site-selective modification in a single step using low concentrations of reagent. Although free cysteines are also modified by the coupling reaction, they can be protected through disulfide formation and then liberated after N-terminal coupling is complete. This allows access to doubly functionalized bioconjugates that can be difficult to access using other methods.
authors: Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.
authors: Allie C
authors: AC
authors: Obermeyer
authors: John B
authors: JB
authors: Jarman
authors: Matthew B
authors: MB
authors: Francis
mesh_terms: D000627:Aminophenols / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D000627:Aminophenols; D010455:Peptides; D011506:Proteins; C027667:2-aminophenol; D011392:Proline