Amino acids analogues

This carboxyborane can undergo an amine exchange reaction with Hquid ammonia (eq. 7) to yield the boron analogue of glycine, the simplest alpha-amino acid (13). There has been a great deal of work on the pharmacological activity of these amino acid analogues (14). 

Amine boranes have been examined by a variety of spectroscopic methods (24—29). The boron-substituted alpha-amino acids have been utilized in animal model studies. These compounds along with their precursors and selected derivatives have been shown to possess antineoplastic, antiarthritic, and hypolipidemic activity (30—32). The boron amino acid analogues are also being evaluated for possible utility in boron neutron capture therapy (BNCT) (33). 

Hightower, L.E. (1980). Cultured animal cells exposed to amino acid analogues or puromucin rapidly synthesize several polypeptides. J. Cell. Physiol. 102, 407-427. 

Kelley, P.M. Schlesinger, M.J. (1978). The effect of amino acid analogues and heat shock gene expression in chicken embryo fibroblasts. Cell 15, 1277-1286. 

D-cycloserine An amino acid analogue of D-serine that has been reported to show benefits in treating the negative symptoms of schizophrenia. 

Capping Croups as Amino Acid Analogues and Dipeptide Mimetics... 

Aside from these relatively direct applications of site-directed mutagenesis, combination of recombinant DNA techniques with other experimental strategies will no doubt prove to be of increasing importance. If the gene of interest can be expressed with sufficient efficiency in auxotrophs, then proteins in which selected amino acids are isotopically enriched [12] may be produced to increase the sensitivity and selectivity of magnetic resonance techniques. Alternatively, amino acid analogues that are recognized as substrates by aminoacyl tRNA synthetases may be incorporated randomly in place of the true substrate amino... 

Yu X, Imam SZ, Newport GD, Slikker W Jr, Ali SF. (1999). Ibogaine blocked methamphetamine-induced hyperthermia and induction of heat shock protein in mice. Brain Res. 823(1-2) 213-16. Zaczek R, Coyle JT. (1982). Excitatory amino acid analogues neurotoxicity and seizures. Neuropharmacology. 21(1) 15-26. 

Peter, A. et al.. High-performance liquid chromatographic separation of the enantiomers of unusual a-amino acid analogues, J. Chromatogr. A, 871, 105, 2000. 

Peter, A. et al., A comparison of the direct and indirect LC methods for separating enantiomers of unusual glycine and alanine amino acid analogues, Chromatographia, 56, S79, 2002. 

An analogous method was used by Endo and colleagues in a-amination of unreactive carboxylic acids. Treatment of iV-acylhydroxylamine O-carbamates 92 by KHMDS or LDA followed by [3,3]-sigmatropic rearrangement and decarboxylation provided a-amino acid analogues 93 (equation 29). 

Somatostatin has a very brief half-life in serum and is not useful clinically. An 8-amino acid analogue with 2 D-amino acids substituted for the naturally occurring L-amino acids is more stable, and monthly injections of a depot form of this analogue (octreotide, Sandostatin LAR) have several uses. Long-acting octreotide is used to treat acromegaly, as described earlier. It is also used to counteract unpleasant effects caused by overproduction of secreted bioactive substances produced by neuroendocrine tumors, including hyperinsulinemia from insulinomas and secretions from carcinoid tumors that cause severe diarrhea. Octreotide may also control severe diarrhea associated with AIDS that has not responded to other treatments. 

The numerous applications of fluorinated amino acids in medicinal chemistry and in enzymology have induced a large number of studies dedicated to their synthesis. Synthetic chemists have provided protein biologists and chemists with an incredible range of fluorinated amino acids. Since this work has been covered in the literamre, we only review some representative examples of proteogenic fluorinated amino acid analogues, with special focus on the synthetic aspects proper to fluorine chemistry. The numerous fluorinated peptidomimetic units (e.g., amino alcohols) are not included in this chapter. 

Different syntheses of y-amino-/3-ketoeter derivatives from iV-protected L-aminoacids by Al,Al -carbonyldiimidazole activation and treatment with the magnesium enolate of hydrogen ethyl malonate are described. These compounds are useful intermediates in the preparation of active amino acid analogues, as illustrated and summarized in equation 103. 

Closely related in topographical structure, but with different and quite unique torsional properties, are the (3-isopropyl-substituted analogues of tyrosine 41,421 and phenylalanine. 43,441 All four isomers of each amino acid analogue have been prepared by asymmetric synthesis. In addition, the highly topographically constrained amino acid 3-isopropyl-2, 6 -dimethyl-tyrosine has been prepared by asymmetric synthesis/451... 

The biological properties of phosphorus amino acid analogues (and their derivatives) depend upon their stereochemistry. Consequently, numerous methods for obtaining these compounds in stereochemically pure form have been developed. Two excellent review articles summarize the work performed prior to 1993. 3,4 Resolution of racemates continues to be a useful approach for obtaining optically pure aminoalkylphosphonic and -phosphinic acid derivatives (vide infra), but most of the newer literature describes asymmetric syntheses of these compounds.15-17 Two methods for resolution and one for asymmetric synthesis are described (vide infra) they have been selected since they are relatively easy to perform, work with a variety of side chains, can be carried out on a reasonable scale with readily available starting materials, and produce products of high stereopurity. However, just as in traditional amino acid chemistry, each side chain introduces its own complications, and in many cases, especially for more complex analogues, other methods may be preferred. 

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