Aminoacyl groups

Vilsmeier-Haack conditions have been used most frequently for formylation but are also applicable to longer acyl chains[3]. Reactions with lactams generate 3-(iminyl)indoles which can be hydrolysed to generate co-aminoacyl groups as in equation 11.6 [4]. 

An interest in ester migration in the monoacyl derivatives of the vicinal-diol grouping in ribofuranosides stemmed from a desire to establish the position of attachment of the aminoacyl group to the terminal adenosine residue of aminoacyl-(t-RNA),569-571 and also from the necessity of producing suitably protected intermediates for oligoribonucleotide syntheses. That a facile equilibrium can exist is shown by the fact that, on being kept, an ethanol solution of... 

Unlike penicillins and cephalosporins, which have a side aminoacyl group joined to the beta-lactam ring, imipenem has a a-hydroxyethyl side chain. Significant resistance to hydrolysis by beta-lactamases is observed in this compound, evidently thanks to the fran -configuration of the side chain, while the side chain of penicillins and cephalosporins have a cis-configuration. 

A11 aminoacyl groups were introduced into 2-0- and 3-0- positions of methyl a-D-glucopyianoside. 

MECHANISM FIGURE 27-14 Aminoacylation of tRNA by aminoacyl-tRNA synthetases. Step is formation of an aminoacyl adenylate, which remains bound to the active site. In the second step the aminoacyl group is transferred to the tRNA. The mechanism of this step is somewhat different for the two classes of aminoacyl-tRNA synthetases (see Table 27-7). For class I enzymes, (2a) the aminoacyl group is transferred initially to the 2 -hydroxyl group of the 3 -terminal A residue, then (3a) to the 3 -hydroxyl group by a transesterification reaction. For class II enzymes, ( the... 

While peptide antibiotics are synthesized according to enzyme-controlled polymerization patterns, both proteins and nucleic acids are made by template mechanisms. Tire sequence of their monomer emits is determined by genetically encoded information. A key reaction in the formation of proteins is the transfer of activated aminoacyl groups to molecules of tRNA (Eq. 17-36). Tire tRNAs act as carriers or adapters as explained in detail in Chapter 29. Each aminoacyl-tRNA synthetase must recognize the correct tRNA and attach the correct amino acid to it. The tRNA then carries the activated amino acid to a ribosome, where it is placed, at the correct moment, in the active site. Peptidyltransferase, using a transacylation reaction, in an insertion mechanism transfers the C terminus of the growing peptide chain onto the amino group of... 

The anticodon of the tRNA is base-paired with mRNA in the "decoding site" on the 30S subunit. The 3-CCA end with attached aminoacyl group lies in the peptidyltransferase site in the 50S subunit. (F) and (G) are courtesy of Cate et al.18... 

A careful stereochemical analysis has led to the conclusion that for all of the different aminoacyl groups to be able to react in the same way at the peptidyltransferase site and to all generate trans amide linkages, the torsion angles < ) and q/ of the resulting peptide must be approximately those of an a helix.388 Thus, the peptide emerging from the ribosome exit tunnel may be largely helical. 

Write out in detail, using structural formulas, the chemical mechanism of synthesis of an aminoacyl-tRNA and of incorporation of the aminoacyl group into a peptide chain being formed by a ribosome. 

Synthases differ with respect to their site of attachment to tRNA. Some synthases form the 2 ester, some form the 3 ester, and still others produce a mixture of the two. The specificity of the synthases was determined by analyzing their ability to act on tRNA derivatives lacking one or the other terminal hydroxyl group. Once esterified to the terminal ribose, the aminoacyl group can migrate between the vicinal 2 and 3 hydroxyl groups. Thus, in cells, amino-acyl-tRNAs are mixtures of 2 and 3 esters. Only the 3 derivative is a substrate for the subsequent transpeptidation reaction catalyzed by the ribosome. 

In the second step, without leaving the enzyme, the aminoacyl group of aminoacyl-AMP is transferred to the 3 end of the tRNA molecule to form aminoacyl-tRNA ... 

The appropriate pam resin (tBoc-aminoacyl-(4-carboxyamidomethyl)-benzylester-poly-(styrene-l% divinylbenzene), where the aminoacyl group is the protected C-terminal amino acid corresponding to the C-terminal residue in the chemokine to be synthesized. 

The attachment of an amino acid to an appropriate tRNA is accomplished via aminoacyl-tRNA synthetase and the hydrolysis of ATP. There is a separate enzyme specific for each amino acid, and it will recognize all tRNAs for that amino acid. The reaction proceeds in two steps and requires Mg2+ (Fig. 17-8). The first step, amino acid activation, results in the formation of an aminoacyl-AMP-enzyme intermediate. In the second step, the aminoacyl group is transferred to its appropriate (cognate) tRNA, the amino acid being linked to tRNA through an ester bond. It appears that recognition between the synthetase and tRNA is achieved through very precise contact between the... 

Figure 3 Biosynthetic pathways. (A) In the terpenoid coupling reaction, isomers of isopentenyl pyrophosphate are joined with the loss of pyrophosphate, leading to a linear intermediate that is cyclized to a terpenoid skeleton, as shown for the diterpene taxol. (B) In the polysaccharide coupling reaction, hexose and pentose monomers are joined with the loss of a nucleoside diphosphate, as shown for the epivancosaminyl-glucose disaccharide of vancomycin. (C) In the first step of the nonribosomal peptide coupling reaction, an aminoacyl adenylate is transferred to a carrier protein or thiolation domain (denoted T ) with loss of adenosine monophosphate. In the second step, this carrier protein-tethered aminoacyl group is coupled to the amine of an aminoacyl cosubstrate, forming a peptide bond, as shown for two residues in backbone of vancomycin. (D) In the polyketide coupling reaction, the loss of carbon dioxide from a two or three-carbon monomer yields a thioester enolate that attacks a carrier protein-tethered intermediate, forming a carbon-carbon bond as shown for the polyketone precursor of enterocin.

The use of azido acids for the introduction of aminoacyl groups eliminates the need of protecting the amino group during the acylation. The azidoacyl derivatives obtained are reduced directly to the aminoacyl ones. This method was used in the preparation of aminopenicillins (19) from azidoacyl chlorides and 6-aminopenicillanic acid, Azido-... 

In orthoesters (458 Scheme 84) one alkoxy group can be replaced by aminoacyl groups, by aminosul-fonyl groups or by the 1-imidazolyl group on reaction with ureas,imides, salicylamide, N-alkylsulfonamides in the presence of Lewis acids or with imidazoles under acid cat ysis. Excess aryl isocyanates convert orthoformates to acetals of parabanic acid. ... 

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