N-Terminal Modification of Proteins with o-Aminophenols

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• 作者：Allie C. Obermeyer ; John B. Jarman ; Matthew B. Francis
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：July 9, 2014
• 年：2014
• 卷：136
• 期：27
• 页码：9572-9579
• 全文大小：449K
• ISSN：1520-5126

文摘

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.