Functionalization of Amino Acids

A rather obvious approach to prepare functionalized amino acids is to begin with another amino acid. Most transformations involve conversion of chiral, nonracemic a-amino acids to chiral, nonracemic non-a-amino acids and these approaches will be discussed in chapter five. There are several procedures that generate functionality in 

There are many other sequences that use chiral, racemic amino acid precursors to prepare substituted non-a-amino acids. This section wUl focus on those methods that manipulate and/or add to the functionality of an existing amino acid to produce a new amino acid. As mentioned above, diastereoselective and enantioselective transformations of chiral, nonracemic amino acids will be discussed in chapter five, section S.l. 

The acyl carbon of readily available amino acids such as alanine can be converted to a ketone moiety by activation of the acid with carbonyl diimidazole (CDI) and then condensation with an enolate, such as the magnesium enolate of malonic acid, mono ethyl ester. In this particular example, N-Boc alanine was converted to 1.206 using this method O Catalytic hydrogenation of the ketone moiety gave the alcohol group in 1.207, and conversion to the chloride and base induced dehydrohalogen-ation gave ethyl 4-(N-Boc amino)pent-2-enoate (7.205). 

An unusual procedure reacted ethanolamine with -alanine (3-aminopropanoic acid). Apparently, the reaction proceeds via formation of an enamine, which reacted with P-alanine to give 1.209 (2-aminomethyl-4-aminobutanoic acid). The yield 

A more widely used amino acid is Y-aminobutyric acid (GABA, 4-aminobutanoic acid), along with its synthetic derivatives. This stems from the fact that GABA is a mammalian neural transmitter (see chapter six, section 6.1) and preparation of GABA and analogs has received quite a bit of synthetic attention. 

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Table 1.2 Reactive functionality of amino acid residues frequently present in proteins...

The amino acids falling into each category are presented in Table 8.9. The pathways in processes (i) and (ii) are described in Appendix 8.3. The combined process of deamination plus transamination illustrates important principles in amino acid catabolism. These lead to an appreciation of some of the biochemical and physiological functions of amino acids that are important in health and disease. 

Part 6 concludes with two brief, informative supplements that integrate physiological and biochemical principles as they apply to the nonmetabolic functions of amino acids and lipids Supplement 1 —Principles of Physiology and Biochemistry Neurotransmission and Supplement 2—Principles of Physiology and Biochemistry Vision. 

Depending on the nature of the protein and the protease used, progressive proteolysis can liberate bitter peptides from proteins, the bitterness of which is a function of amino acid composition and sequence as well as the peptide chain length (Adler-Nissen, 1986b). An excellent review of the chemistry of bitterness has been published (Roy, 1997) and the reader is directed to this for more details. 

Triethylstannyl and tributylstannyl esters are prepared for temporary protection of the carboxy function of amino acids.P P l Stannyl esters of N-protected amino acids are stable to anhydrous amines as well as to water and alcohols. Aqueous amines convert them into the ammonium salts. Stannyl esters of N-unprotected amino acids are cleaved in quantitative... 

The three-dimensional structure of many enzyme molecules, including hydrolytic enzymes such as lysozyme, chymotrypsin, ribonuclease, carboxypeptidase A, elastase, and papain, has been determined in recent years throu] the X-ray diffraction method, and the steric arrangement and function of amino acid residues at the active site has been elucidated (/). 

Alkyl-type protecting groups, protecting groups for the amino function of amino acids during peptide synthesis based on alkyl moieties. The most popular protect-... 

An elegant in situ protection-activation strategy usingBF3-Et20 has been described for the functionalization of amino acids, leading to the facile preparation of amides (including dipeptides) of the carboxylic acid, circumventing the need to protect-deprotect the amino moiety (eq 54). ... 

In terms of amount used, the most important function of amino acids is to provide building blocks for the synthesis of proteins in the body. It is estimated that about 75% of amino acid utilization in a normal, healthy adult is for this function. The maintenance of body proteins must occur constantly in the body because tissue proteins break down regularly from normal wear and tear, as well as from diseases and injuries. The amino acids used in this maintenance come from proteins that are eaten and hydrolyzed during digestion, from the body s own degraded tissue, and from the synthesis in the liver of certain amino acids. The amino acids from these three sources constitute what is called the amino acid pool of the body. This cellular supply of amino acids is constantly being restocked to allow the synthesis of new proteins and other necessary metabolic processes to take place as needed. 

Figure 1 Protein functionalization of amino acid side chains of cysteine (Cys), lysine (Lys), tyrosine (Tyr), and glutamine (Gin). Reprinted with permission from Thordarson, P. Le Droumaguet, B. Velonia, K. Appl. Microbiol. Biotechnol. 2006, 73,243-254. Copyright 2006 Springer-Verlag.

Figure 13 Illustration of the concept applying PEO-peptide conjugates as specific solubilizers to render inhibitors of IspE water soluble. The peptide segment modulates interactions with the inhibitor and the PEO block provides water solubility (F1.4 indicate side-chain functionalities of amino acids). Reprinted with permission from Hirsch, A. K. H. ...

Contrary to the principles of the ribosomal protein biosynthesis, where the carboxylic functions of amino acids are reactively bound to a polymer — the transfer ribonucleic acid (t-RNA) — which itself is orientated specifically on the ribosomal messenger ribonucleic acid (m-RNA) (Fig. 1 for details see [36]), the basic idea of the Merrifield synthesis depends upon a nonreactive covalent fixation of the C-terminal amino acid of the target peptide on a solid support (Fig. 2). On this insoluble but swollen polymer, the pep-... 

The amino acid overproduction is also a function of amino acid secreted out of the cell. This can be achieved by overexpressing amino acid carrier proteins which increases amino acid efflux and relieves feedback inhibition. 

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