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Modified proteins from an expanded genetic code
Edward R. Winstead


Japanese scientists have developed a method for producing novel proteins not found in nature. The new molecules contain artificially created amino acids—the structural components of proteins—derived from DNA that includes a new pair of chemical bases added by the researchers. The ultimate aim of the project is to develop efficient methods for engineering proteins for industrial uses as well as applications in medicine.

Detail of the unnatural molecule structures. View larger

Demonstrating the potential of the strategy, the researchers created a close chemical relative, or analog, of the amino acid tyrosine, and introduced it into a protein. One of the technical challenges was to make sure that the amino acid inserted at the intended location and that the new chemical bases paired appropriately during the cellular process in which DNA is transformed into proteins.

The instructions for making proteins are contained in the sequence of DNA. DNA's four chemical bases—known by the letters A, T, C, and G—form 64 distinct three-base arrangements in nature. Each arrangement (e.g., AUC, CAG, AGG) corresponds to a specific amino acid—the structures that make up proteins. In this study, the researchers created novel amino acids by adding two chemical bases, called s and y, to the genetic code.

Ichiro Hirao, of the Yokoyama CytoLogic Project, in Saitama, Japan, led the research. The "system described here should contribute to the development of a general method for the site-specific incorporation of unnatural amino acids into proteins," the researchers write in Nature Biotechnology.

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Hirao, I. et al. An unnatural base pair for incorporating amino acid analogs into proteins. Nat Biotechnol 20, 177-181 (February 2002).

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