Carboxyl group amino acids component

The amino acid components of peptides and proteins are linked together by amide bonds (see p. 60) between a-carboxyl and a-amino groups. This type of bonding is therefore also known as peptide bonding. In the dipeptide shown here, the serine residue has a free ammonium group, while the carboxylate group in alanine is free. Since the amino acid with the free NHs group is named first, the peptide is known as seryl alanine, or in abbreviated form Ser-Ala or SA. 

Peptide chains have a direction and therefore two different ends. The amino terminus (N terminus) of a peptide has a free ammonium group, while the carboxy terminus (C terminus) is formed by the carboxylate group of the last amino acid. In peptides and proteins, the amino acid components are usually linked in linear fashion. To express the sequence of a peptide, it is therefore suf cient to combine the three-letter or single-letter abbreviations for the amino acid residues (see p. 60). This sequence always starts at the N terminus. For... 

Mixed anhydride method, a procedure of peptide coupling using reactive species resulting from the carboxylic moiety of a N-acylated amino acid and alkyl chlorocar-bonates (alkyl chloroformates), especially isobutyl chlorocarbonate (isobutyl chloro-formate), that readily reacts with an amino component. The nucleophilic amino component attacks the carboxy group of the amino acid component, with formation of the desired peptide derivative and release of the unstable isobutyl carbonic acid which immediately decomposes into carbon dioxide and isobutanol [J. Meienhofer, in The Peptides Analysis, Synthesis, Biology,... 

Remarkably, nearly half of the amino acid components are L-a-amino-isobutyric acid residues (Aib), an amino acid not present in ribosome-manufactured proteins (p. 8). Peptides containing Aib-residues have been recognized to form a-helices particularly readily, an explanation of the pore forming properties of alamethicins and of similar natural and artificial polypeptides. In the natural analogs alanine or valine is found to be replaced by Aib closely related natural compounds are among others, suzukacillin, trichotoxin (mould products), and less similar, a component of bee venom, the 25-peptide mellitin. In the synthesis of peptides containing a-amino-isobutyric acid certain difficulties are encountered due to the poor steric accessibility of the amino—as well as of the carboxyl group. 

Wool has a complex chemical stmcture, composed mainly of a large number of different proteins (87). It is amphoteric in character because of the presence of basic amino and acidic carboxyl groups in the side chains of some of the component amino acids. In an aqueous acidic dyebath, protonation of the amino and carboxyl groups results in a net positive charge on the fiber. 

The chemical properties of peptides and proteins are most easily considered in terms of the chemistry of their component functional groups. That is, they possess reactive amino and carboxyl termini and they display reactions characteristic of the chemistry of the R groups of their component amino acids. These reactions are familiar to us from Chapter 4 and from the study of organic chemistry and need not be repeated here. 

As has been outlined for the Strecker synthesis, the Ugi reaction also proceeds via initial formation of a Schiff base from an aldehyde and an amine. The imine intermediate is attacked by the isocyanidc, a process which is supported by protonation of the imine by the carboxylic acid component. The resulting a-amino nitrilium intermediate is immediately trapped by the carboxylate to give an 6>-acyl imidiate. All steps up to this stage are reversible. Only the final oxygen to nitrogen acyl shift is irreversible and delivers the A-acyl-a-amino amide as the thermodynamically favored product which contains two amide groups. 

The mechanistic analogy to the Streckcr synthesis becomes obvious in the addition of the isocyanide to the imine to produce the a-amino nitrilium intermediate. Since all four components are involved in this step, it might be expected that every chiral component (chiral groups R1, R2, R3, R4) contributes to diastereofacial differentiation in the nucleophilic attack on the imine. However, in peptide syntheses by four-component condensation5, the chiral isocyanide or a chiral carboxylic acid component has only limited influence on the diastereoselectivity of the a-amino amide formation5. 

The a-amino group of the new aminoacyl-tRNA in the A site carries out a nucleophilic attack on the esterified carboxyl group of the peptidyl-tRNA occupying the P site (peptidyl or polypeptide site). At initiation, this site is occupied by aminoacyl-tRNA mef. This reaction is catalyzed by a peptidyltransferase, a component of the 285 RNA of the 605 ribosomal subunit. This is another example of ribozyme activity and indicates an important—and previously unsuspected—direct role for RNA in protein synthesis (Table 38-3). Because the amino acid on the aminoacyl-tRNA is already activated, no further energy source is required for this reaction. The reaction results in attachment of the growing peptide chain to the tRNA in the A site. 

Amino acids activated at the amino group by a benzotriazolide moiety react with amino acids under elimination of benzotriazole and C02 to give peptides. Reaction is achieved by warming up equimolar amounts of the components in anhydrous acetonitrile or aqueous acetone.[45] The benzotriazolylcarbonylamino acids are prepared from benzo-triazolyl-1-carboxylic acid chloride and amino acids.[46]... 

Another important N-donor group is the amide group. Contrary to the basic amino groups, the more acidic amide functions tend to be deprotonated in the complex and therefore operate as a monoanionic donor. Alkaline conditions promote the deprotonation and subsequent complex formation. The amide group is a very useful component of mixed donor sets, such as N2S2 or N3S, as discussed in the next chapter. Whether a pure amide coordination may occur in M(V) complexes has not yet been proved. Tetrapeptides do form Tc(V) complexes [68], apparently without involvement of the carboxyl group. The N-donor atom provided by Schiflf bases plays only a role in mixed donor sets and will be discussed below. 

A few years later Goebel and Ugi formed a-aminoacid derivatives by the U-4CR with tetra-6)-aIkyl-l-glucopyranosylamines, 58, where any carboxylic acid component can participate. Lehnhoff and Ugi used the U-4CR with 1-amino-2-deoxy-2-Al-acetylamino-3,4,6-tri-6)-acetyl- 3-D-glucopyranose, 59, whose large variety of products could be formed stereoselectively in excellent yields. The desired selective cleavage of the auxiliary groups of these products was equally unefficient. 

There is only a small selection of nonprotein amino acids that contain carbonyl groups in the form of ketone, aldehyde, and carboxylic acid moieties, as part of the side chain. The examples given in Table 6 are components of nonribosomal peptides isolated from bacteria or fungi and siderophores from bacteria. The biosynthesis of these amino acids is not clear however, some of the amino acids with carboxylic acid side chains may be traced back to the L-a-amino acids aspartic acid and glutamic acid. 

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