A Genetically Encoded Boronate-Containing Amino Acid

摘要

Organoboronates have attracted considerable interest as synthetic intermediates for Suzuki cross-coupling reactions, copper catalyzed heteroatom alkylation reactions, asymmetric reductions, Diels-Alder reactions and a variety of other transformations. Boronic acids are also known to form reversible covalent complexes with diols, amino alcohols, amino acids alkoxides, and hydroxa-mic acids. This latter property has been exploited in the synthesis of ligands for the selective recognition of sugars and for the development of potent serine protease inhibitors. In addition, boronates are finding utility as boron neutron capture agents to kill tumor cells. Despite their novel chemical properties, boronic acids are not known to occur naturally in polypeptides, either as posttranslational modifications or as cofactors. Therefore, the ability to genetically encode this functional group would provide useful tools for biomolecular recognition and for the selective chemical modification of proteins. Herein, we describe a general methodology for the site-specific incorporation of p-boronophenylalanine (1) into proteins directly in E. coli (Figure 1). We also demonstrate the utility of this system for boronate-mediated protein modification as well as the single step scarless purification of proteins.