N-Terminal Modification of Proteins with o-Aminophenols
| Autor: | John B. Jarman, Allie C. Obermeyer, Matthew B. Francis |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Proline Stereochemistry Kinetics Chemical biology Peptide Aminophenols 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Coupling reaction Colloid and Surface Chemistry Molecule chemistry.chemical_classification Molecular Structure 010405 organic chemistry Proteins General Chemistry 0104 chemical sciences Amino acid chemistry Reagent Peptides Oxidation-Reduction |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja500728c |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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