Amino acids non-natural

The first step in a strict hierarchical procedure for transforming peptide lead sequences into promising non-peptide analogues generally utilizes the incorpo- 

As shown in Fig. 10, the Grb2 SH2 domain is unique in that the peptide ligand is bound in a type I ft turn conformation, reinforced by an intramolecular hydrogen bond. 

Capping Croups as Amino Acid Analogues and Dipeptide Mimetics 

The hydroxynaphthyl analogue CGP78850 43 was shown to block the epidermal growth factor receptor (EGFR)-Grb2 interaction in living cells. 

A similar terminal-peptide-replacement strategy was used in the Src SH2 domain antagonist program pursued at the Parke-Davis Pharmaceutical Re- 

---

The iodoalanine derivative is available in both enantiomeric forms and this method offers an extremely simple route to large numbers of non-natural amino acids.4 Therefore a reliable and practical method for the synthesis of fully protected iodoalanine 3 in a multigram scale is highly desirable. 

Nokihara K, Gerhardt J Development of an improved automated gas-chromatographic chiral analysis system application to non-natural amino acids and natural protein hydrolysates. Chirality 2001 13 431. 

An attempt was made to synthesize optically active non-natural amino acids by the N, C -coupling reactions of enantiomerically pure natural amino acids with... 

Fig. 1. FTase inhibitors in which amide bonds were replaced by isosteric amines and ethers, and which incorporate non-natural amino acids...

Solid-phase peptide synthesis offers a fast and convenient route for many peptides when isotope-enriched compounds are not required. Classical synthesis additionally permits the use of non-natural amino acids and allows site-specific isotope labeling. Although Fmoc protected 15N-labeled amino adds are commercially available, the cost of such synthesis is usually prohibitive, and the peptides from chemical synthesis require perdeuterated detergents and unfortunately exclude investigation of internal dynamics through measurement of 15N relaxation. 

Busca, P., Paradisi, E., Moynihan, E., Maguire, A.R. and Engel, P.C., Enantioselective synthesis of non-natural amino acids using phenylalanine dehydrogenases modified by site-directed mutagenesis. Org. Biomol. Chem., 2004, 2, 2684. 

Ribosomal Incorporation of Non-Natural Amino Acids Conclusion... 

Figure 10 Alteration of the genetic code for incorporation of non-natural amino acids, (a) In nonsense suppression, the stop codon UAG is decoded by a non-natural tRNA with the anticodon CUA. In vivo decoding of the UAG codon by this tRNA is in competition with termination of protein synthesis by release factor 1 (RFl). Purified in vitro translation systems allow omission of RF1 from the reaction mixture, (b) A new codon-anticodon pair can be created using four-base codons such as GGGU. Crystal structures of these codon-anticodon complexes in the ribosomal decoding center revealed that the C in the third anticodon position interacts with both the third and fourth codon position (purple line) while the extra A in the anticodon loop does not contact the codon.(c) Non-natural base pairs also allow creation of new codon-anticodon pairs. Shown here is the interaction of the base Y with either base X or (hydrogen bonds are indicated by red dashes).

Natural Non-natural amino acid amino acid... 

Chemoselective Ligation - Using Non-natural Amino Acids. 62... 

Post-synthetic functionalization reactions have been reported that make it possible to introduce new groups into folded proteins and peptides using natural [24, 25] as well as non-natural amino acids [26-30]. The disulfide exchange... 

Chemoselective ligation of peptides using the free amino terminal as nucleophile and a thiobenzyl thioester C-terminal amino acid as electrophile provides an efficient approach to the synthesis of proteins with several hundred residues [30]. From this perspective the introduction of non-natural amino acids into proteins becomes a possibility rather than a problem and chemoselective ligation is thus a prospect for the future for the incorporation of new functionality. 

---