L-Configuration, amino acid

Because the amino group is on the a-carbon, the amino acids with this general formula are known as a-amino acids. The a-carbon atom becomes asymmetric when R is not an H atom. Naturally occurring amino acids have an L-configuration. Amino acids are the building blocks of proteins, and the elementary composition of most proteins is similar the approximate percentages are ... 

For instance, the almost exclusive specificity of proteases for L-configurated amino acid derivatives may be destroyed when reactions are carried out in organic solvents [346]. This makes them useful for the synthesis of peptides containing noimatural o-amino acids, which are usually not substrates for proteases. 

Two aPNAs were used in this study, L-CTCCT(b2) as well as its antipode D-CTCCT(b2) made up of unnaturally configured amino acids. A control peptide lacking nucleobases, Ac-Trp-Cys " -Lys-Ser-(Ala2-Lys-Ser)4-Gly-Lys-NH2, was also... 

Ribosomal synthesis of peptides proceeds through translation of messenger ribonucleic acid (mRNA) and utilizes the 20 primary L-a-amino acids. These amino acids are incorporated with the use of specific transfer ribonucleic acid (tRNA) codons. The 20 primary a-amino acids, with the exception of glycine that is achiral, are characterized by an L-configuration at the a-position (Figure 1). In general, most proteins are found to be composed of these 20 L-a-amino acids, as such they are referred to as protein amino acids. 

The extension of the term isotactic to condensation polymers was made by Natta in his first article discussing poly-L-a-amino acids (22). In itself the term isotactic is redundant here as the configuration of the repeating unit is sufficient to identify the macromolecular stmcture. It is, however, useful to distinguish a system, racemic or not, in which each macromolecule is composed of only l or only D residues from a mixture of macromolecules made up of random or alternate sequences of L or d units. Similarly the term syndiotactic serves in the identification of oligopeptides or polypeptides composed of alternate sequences of D and L units, like those synthesized by Lorenzi and Tomasic (77). 

In this chapter, we wiU concentrate mainly on hydroxamate-based siderophores. However, the most representative example of the catechol-based siderophore family is entero-bactin , a highly Cs-symmetric molecule based on a trilactone ring system derived from three L-serine amino acids. The serine amino groups are extended with three catecholic acid units. Enterobactin binds iron(III) in an octahedral coordination of preferred A-cis configuration (see Figure 1 in Section n.C). 

Stereochemistry in Biological Systems. Amino acids occur naturally in both D and L (R and S) enantiomeric configurations. Amino acids that occur in proteins almost always have the L configuration although amino acids that occur in bacterial peptides may have the enantiomeric D configuration. The two configurations are shown in Figure 1.21 for alanine. 

For amino acids the situation is analogous. When the Fischer projection is drawn (carbon chain vertical with most oxidised carbon at the top) all of the natural amino acids found in human proteins are found to have the NHj group on the left-hand side of the Fischer projection and are therefore similar in configuration to l-(—)-glyceraldehyde. These amino acids are consequently known as L-series amino acids (Figure 4.9). 

Figure 2.2. A representative dipeptide made up from L-a-amino acids, in the extended conformation with the amide bond in the trans configuration.

Fischer-Rosanoff convention A method for the specification of absolute configuration, still in common use for amino acids and sugars. When drawn in a Fischer projection with Ci at the top, if the functional group of the specified stereocenter is on the right, the absolute configuration is D, if on the left, it is L. For amino acids, the reference stereocenter is C2 for sugars it is the highest numbered stereocenter [98],... 

If the ring system has a substituent in the 3-position, then the molecule has two asymmetric centers, and two pairs of diastereoisomers are possible (see Fig. 2). The most commonly encountered system is that obtained from the naturally occurring l-a-amino acids. These acids have the S absolute configuration and thus provide the 3S, 8a S structure 79a, which has the hydrogens at positions 3 and 8a cis-diaxially and the 3-substituent pseudoequatorially disposed. This isomer is frequently referred to as the cis isomer and is the mirror image of the dd isomer 79d. Both the dl derivatives, 79b and 79c, are sometimes described as having trans geometry and have the 3-substituent in a pseudoaxial orientation. 

Amino acids are compounds that contain an amino group and a carboxylic acid group. In proteins, the amino acids are always L-a amino acids (the amino group is attached to the a carbon in the L-configuration) (Fig. 5.24). These same amino acids also serve as precursors of nitrogen-containing compounds in the body, such as phosphatidylcholine (see Fig. 5.21) and are the basis of most human amino acid metabolism. However, our metabolic reactions occasionally produce an amino acid that has a (3 or y amino group, such as the neurotransmitter y-aminobutyric acid (see Fig. 5.24). However, only a amino acids are incorporated into proteins. 

A large variety of L- and D-configured amino acids, protected derivatives, and oligopeptides is commercially available from the usual suppliers of chemicals... 

Figure 9.5.4 Model of a tubular stack of cyclic peptides. Note the presence of l- and D-configured amino acids. (From Ghadiri et al., 1992.)...

The ordered structures of proteins (alpha-helices, beta-sheexs) readily explain the fact that all protein molecules (on Earth at least) are comprised of L-a-amino acids (since an occasional D-amino add would disrupt the ordered structure of L-enantiomers). The configurations of L-amino acids are described by the structure below they are consistent with carbohydrate nomenclature as seen by comparison with the D-glyceraldehyde structure shown earlier in this chapter. In both classes. 

Of the number of chromophoric derivatives of chiral amines for potential use in the establishment of their absolute configuration by BCD measurement only a few have proven to be generally useful. Of these, intensive investigation of the Af-salicylidene (Schiff base) derivatives of chiral primary amines, including unsubstituted and ring-substituted a- and S-arylalkylamines, a-amino acids, unsaturated and satnrated aliphatic and alicyclic amines, and amino sugars, has resulted in the formulation of the salicylidenamino chirality rule ° °. The application of this rule has recently been reviewed and has been successfully used for the establishment of absolute configuration of chiral primary amines in connection with other stereochemical studies. In related studies, the conformations of a series of pyridoxyl-L-a-amino acid Schiff bases were deduced from their CD spectra ... 

The collective effects of the double-bond character of the peptide bond, the intramolecular hydrogen bonding, the hydrophobic bonding, and the L configuration of the peptide residues induce most poly(L-a-amino acids) and protein sequences to adopt the shape of a right-handed a-helix. But there are also exceptions. Despite the l configuration of the peptide residues, poly(L-j8-benzyl aspartate) forms a left-handed a helix. In addition to a helices and the pleated-sheet structures 03 structures), other secondary structures are also known for poly(a-amino acids) (Table 30-2). 

In general, naturally occurring (IV-protected) L-amino acid esters of short-chain alcohols, such as methyl and ethyl esters are usually sufficiently reactive as acceptors to achieve reasonable reaction rates in enzymatic peptide synthesis via aminolysis. For less reactive (nonnatural) analogs, such as a-substituted [313] or D-configured amino acids [314], activated esters are recommended, among them, 2-haloethyl (e.g., 2-chloroethyl, trifluoroethyl) [315], p-nitrophenyl [316], or guanidinophenyl esters [317]. For the use of cyclic activated esters [5(47/)-oxazolones] see below. 

In all reactions, the first stage is formation of SchifTs base a by condensation of PalP and the amino acid. Schiff s bases a and b represent part of transamination, but for the complete mechanism see Transamination. Racemization a- b, followed by b-ia-iamino acid-1-PalP, with addition of the proton in the opposite configuration. Amino acid decarboxylation a -> d- c - amine + PalP. Serine hydroxymethyltransferase (EC 2.1.2.1) X = OH L-serine + PalP a f- g glycine + PalP reversal of these reactions leads to L-serine synthesis from glycine the hydroxymethyl group is carried by te-trahydrofolic acid. Cysteine desulfhydrase (EC 4.4.1.1) X = SH cy eine + PalP a b-> c-y hydro-... 

Polymers 7o(D) and 7e(L) bear amino acid pendants In D-and L- configurations, respectively. 

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