Genetic Code Expanding

Nediljko B., Engineering the Genetic Code Expanding the Amino Acid Repertoire for the Design of Novel Proteins, Wiley, New York, 2006. 

Budisa N (2006) Engineering the genetic code expanding the amino acid repertoire for the design of novel proteins. Wiley-VCH, New York... 

Wang L, Xie J, Schultz PG (2006) Expanding the genetic code. Annu Rev Biophys Biomol... 

Table 12.1. The genetic code presented in this table is very nearly universal. There are isolated exceptions in the genome of mitochondria, which is described later in this chapter. Beyond that, the genetic code has been expanded to include codons for two unusual amino acids that occur in a modest number of proteins. These amino acids are selenomethionine, in which an atom of selenium replaces the sulfur atom of methionine, and pyrrolysine, a cychzed form of lysine. For details, see A. Ambrogelly, S. Palioura, and D. Soil, Nat Chem Biol 3 29-35 (2007). 

V.W. Cornish, D. Mendel, P.G. Schultz, Probing protein stmcture and function with an expanded genetic code, Angew. Chem. Int. Ed. 34(6) (1995) 621-633. 

J.C. Anderson, N. Wu, S.W. Santoro, V. Lakshman, D.S. King, P.G. Schultz, An expanded genetic code with a functional quadmplet codon, Proc. Natl. Acad. Sci. USA 101(20) (2004) 7566-7571. 

Despite the fact that only 20 amino acids (plus selenocys-teine and formylmethionine in prokaryotic systems) are known to be directly specified by the genetic code, chemical analysis of mature proteins has revealed hundreds of different amino acids, all of them structural variants on the original 20. This structural diversity, which greatly expands the chemical lexicon of proteins, results from posttranslational modification of the primary products of translation. Our knowledge of the nature and significance of enzymatic reactions that bring about these important alterations is still very incomplete. 

Chung, H.-H., Benson, D. R., and Schultz, P. G. (1993). Probing the structure and mechanism of ras protein with an expanded genetic code. Science 259, 806-809. 

Expanding the Genetic Code Through Chemical Biology Protein Syndiesis, Key Reactions of Protein-Nucleic Acid Interactions Translation An Overview... 

Proteins Structure, Function, and Stability Expanding the Genetic Code Through Chemical Biology Synthetic Proteins, Design and Engineering of Phage Display... 

Xie J, Schultz PG. A chemical toolkit for proteins—an expanded genetic code. Nat. Rev. Mol. Cell Biol. 2006 7 775-782. 

Expanding the Genetic Code Through Chemical Biology Metallo-enzymes and Metallo-Proteins, Chemistry of Proteins, in vivo Chemical Modification of... 

Budisa N. Prolegomena to future experimental efforts on genetic code engineering by expanding its amino acid repertoire. Angew. Chem. Int. Ed. Engl. 2004 43 6426-6463. 

Wang L, Brock A, Herberich B, Schultz PG. Expanding the genetic code of escherichia coU. Science 2001 292 498-500. 

Chin JW, Cropp TA, Anderson JC, Mukherji M, Zhang Z, Schultz PG. An expanded eukaryotic genetic code. Science 2003 301 964-967. 

RNAs that employ the four standard bases have more limited opportunities for hydrogen-bonding interactions and functionality, even though the range of tertiary interactions is broad (63). The use of additional base pairs would not only increase the stmctural complexity of RNA but would also allow for enzymatic replication. This concept has been exploited by several research groups to expand the genetic code, as well as to generate novel, site-specihcally modihed RNAs (e.g., biotinylated, huorescent, cross-linked RNAs) (6, 29, 64). 

By analogy to the terms co- and posttranslational modifications of peptides and proteins to define these transformations in the in vivo biosynthesis, chemical manipulations at least theoretically can be carried out in a co- or postsynthetic manner. While nature exploits the sequence- and even conformation-dependent regioselectivity of enzymes to expand the molecular and functional diversity of peptides and proteins beyond the genetic code,P l synthetic chemical reactions are insufficient for the required selectivity even with the most advanced conjugation techniques. Therefore, the tactics usually employed involves a cosynthetic approach, i.e. synthesis of polypeptide chains with annino acid derivatives or... 

The genetic code only allows for two types of base-pair, A with T and G with C. There have been attempts to prepare nucleoside analogues to expand the... 

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