Amino acids noncanonical

Dieterich DC, Link AJ, Graumann J et al (2006) Selective identification of newly synthesized proteins in mammalian cells using bioorthogonal noncanonical amino acid tagging (BONCAT). Proc Natl Acad Sci USA 103 9482-9487... 

The activity of PK and NRPSs is often precluded and/or followed by actions upon the natural products by modifying enzymes. There exists a first level of diversity in which the monomers for respective synthases must be created. For instance, in the case of many NRPs, noncanonical amino acids must be biosynthesized by a series of enzymes found within the biosynthetic gene cluster in order for the peptides to be available for elongation by the NRPS. A second level of molecular diversity comes into play via post-synthase modification. Examples of these activities include macrocyclization, heterocyclization, aromatization, methylation, oxidation, reduction, halogenation, and glycosylation. Finally, a third level of diversity can occur in which molecules from disparate secondary metabolic pathways may interact, such as the modification of a natural product by an isoprenoid oligomer. Here, we will cover only a small subsection of... 

The ability to alter protein structure and function by introducing noncanonical amino acids has great potential to enhance the understanding of proteins, to generate new tools for biomedical research, and to create novel therapeutic... 

The first criterion for a candidate tRNA to be used as a delivery vehicle for noncanonical amino acids is the ability to insert its appended amino acid site specifically into a target protein. An obvious route is redefining existing codons to encode the noncanonical residue. Rather than using a cis sequence element... 

The addition of a non-canonical amino acid to the genetic code requires - in the first case - additional components of the protein producing system a noncanonical amino acid, an exogenous tRNA/aminoacyl-tRNA synthetase pair, and an unique codon that specifies the amino acid of interest. Orthogonality between the exogenous translational components (Scheme 1-30) and their endogenous opposite numbers is the key feature of this approach. With the effect... 

Aminopropionic acid is noncanonical amino acid and chemical precursor. 

Noncanonical Amino Acids in Peptide/Protein Engineering... 

In nature the 20 proteinogenetic standard (or natural) a-amino acids that are directly encoded by the genetic code are the building blocks of all proteins within humans and other eukaryotes. Amino acids that are not among these standard amino acids are named noncanonical amino acids, nonstandard or unnatural amino acids. 

Expanding the Scope of Protein Chemistry Noncanonical Amino Acids... 

Figure 19 Representative set of noncanonical amino acids that have been incorporated into proteins in cells. Amino acids shown in black are incorporated by cells that are auxotrophic for the canonical amino acid, but are otherwise wild type . Amino acids shown in blue require overexpression of the wild-type aminoacyl-tRNA synthetase. Amino acids shown in green require expression of an editing-impaired aminoacyl-tRNA synthetase. Analogs drawn in red require expression of a synthetase with an engineered substrate-binding pocket.

Several strategies exist for incorporating noncanonical amino acids into proteins.One powerfiil approach uses stop, or nonsense, codons that normally terminate protein translation. Suppressor tRNAs recognize stop codons and suppress translational termination. By linking a noncanonical amino acid to a suppressor tRNA by chemical misacylation, one can insert the new amino acid in vitro in response to a stop codon. " To accomplish the same objective in vivo, however, an aminoacyl-tRNA synthetase that recognizes and couples the suppressor and the noncanonical amino acid must be developed. This method enables insertion of a single noncanonical amino acid at a specified position in a protein. 

PIS 15] Piscotta F.J., Tharp J.M., Liu W.R. et al, Expanding the chemical diversity of lasso peptide MccJ25 with genetically encoded noncanonical amino acids , Chemical Communications, vol. 51, pp. 409—412, 2015. 

Liu, W. Incorporation of two different noncanonical amino acids into a single protein. 

Wu, B. Wang, Z. Huang, Y Liu, W. R. Catalyst-free and site-specific one-pot dual-labeling of a protein directed by two genetically incorporated noncanonical amino acids. ChemBioChem 2012,13, 1405-1408. 

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