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Expanding the genetic code--TSRI scientists synthesize 21-amino-acid bacterium

ghtly modified versions of the amino acids cysteine and lysine.

These rare exceptions aside, scientists have often looked for ways to incorporate other unusual amino acids into proteins because such technologies are of great utility for medical research. For example, many proteins used therapeutically need to be modified with chemical groups such as polymers, crosslinking agents and cytotoxic molecules. This technology will also be useful in basic biomedical research. For example, there are novel amino acids that contain fluorescent groups that can be used to label proteins and observe them in vivo. Other groups contain photoaffinity labels that could be used for covalently cross-linking proteins to one another. This allows scientists to see what the proteins interact with in living cells--even weak interactions that are difficult to detect by current methods.

Novel hydrophobic amino acids, heavy metal-binding amino acids, and amino acids that contain spin labels could be useful for probing the structures of proteins into which they are inserted. And unusual amino acids that contain chemical moieties like "keto" groups, which are like LEGO blocks, could be used to attach other chemicals such as sugar molecules, which would be relevant to the production of therapeutic proteins.

While inserting novel amino acids inside proteins is nothing new, in the past such modifications had to be carried out in the test tube, with the scientist doing all the manipulations by hand. Now, the 21-amino-acid bacterium uses its own "hands" to make the modified proteins.

The Basis of the Technology

Schultz and his colleagues succeeded in making the 21-amino-acid bacteria by exploiting the redundancy of the genetic code.

When a protein is expressed, an enzyme reads the DNA bases of a gene (A, G, C, and T), and transcribes them into RNA (A, G, C, and U). This so-called "messenger RNA" is then translated by another proteinRNA comple
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
14-Jan-2003


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