Elongation reaction

The following short descriptions of the steps involved in the synthesis of a tripeptide will demonstrate the complexity of the problem amino acid units. In the later parts of this section we shall describe actual syntheses of well defined oligopeptides by linear elongation reactions and of less well defined polypeptides by fragment condensation. 

The elongation reactions are repeated until the growing chain reaches 16 carbons in length (palmitic acid). 

The individual steps in the elongation of the fatty acid chain are quite similar in bacteria, fungi, plants, and animals. The ease of purification of the separate enzymes from bacteria and plants made it possible in the beginning to sort out each step in the pathway, and then by extension to see the pattern of biosynthesis in animals. The reactions are summarized in Figure 25.7. The elongation reactions begin with the formation of acetyl-ACP and malonyl-ACP, which... 

As seen already, palmitate is the primary product of the fatty acid synthase. Cells synthesize many other fatty acids. Shorter chains are easily made if the chain is released before reaching 16 carbons in length. Longer chains are made through special elongation reactions, which occur both in the mitochondria and at the surface of the endoplasmic reticulum. The ER reactions are actually quite similar to those we have just discussed addition of two-carbon units... 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

This device is a generically simple reactor comprising a micro-channel Y-piece section and an elongated reaction micro channel attached [26, 27]. The microstructures were mechanically fabricated in PMMA using a flat end mill. A top plate was joined with the microstructured plate by baking under vacuum. The reaction temperature was fixed using a hot-plate. 

Once fatty acids have been made 16 carbons long, they can be lengthened by adding 2 carbon atoms at a time with malonyl-CoA in a reaction that looks a lot like the first step of fatty acid synthesis. However, the elongation reaction is carried out on the fatty acyl-CoA and by an enzyme that is different from fatty acid synthase.4 ... 

The first comparison of the kinetics of E-site GTP hydrolysis and microtubule elongation was carried out by MacNeal and Purich (1978a). Their results indicated that the hydrolysis and elongation reactions were coupled because there was only a very slight lag in the hydrolytic process at the concentrations of microtubule protein employed. These data do not distinguish between two mechanistic alternatives ... 

Other Factors Affecting Microtubule Elongation Reactions... 

The Elongation Reactions in Protein Synthesis Philip Leder... 

Figure 11.11 Outline of the pathway consisting of desaturation and elongation reactions that convert linoleic acid into arachidonic acid.

Figure 20.3 Essential fatty acids in the diet, production of physiological essential acids and their roles in the cell cycle. Essential fatty adds in the diet are mainly linoleic and a-linolenic but they are converted by desaturation and elongation reactions to the essential acids that are used in phospholipid formation and synthesis of eicosanoids. (For details of the elongation and desaturation reactions and eicosanoid formation, see Chapter 11.).

The aldehyde group in 197 bears a potential for C-C bond elongation reactions. For example, 198 was obtained in 89% yield by the reaction with a stabilized ylide as an E-isomer (> 95 5) (Figure 4.9). Additionaly Lewis-acid-mediated reactions are possible. The reaction of the aldehyde 197 with aUyltributyltin and TiCl4 gave the homoallylic alcohol 199 in 86% yield. 

On confirming that the ninhydrin test is negative, the resin is subjected to the segment elongation reaction. If the ninhydrin test is positive, the same coupling procedure should be repeated until the ninhydrin test becomes negative. 

When carrying out the elongation reactions with fully protected segments, it is important to compare the difference in solubility between the amino and carboxy components. If the difference in solubility is significant, the more soluble component must be used in slight excess, up to 1.1 equivalents, versus the less soluble component. This process is particularly effective in making purification of the product easier. 

Three Elongation Reactions Are Repeated with the Incorporation of Each Amino Acid Two GTPs Are Required for Each Step in Elongation... 

Overview of reactions in protein synthesis. (aab aa2, aa3 = amino acids l, 2, 3.) Protein synthesis requires transfer RNAs for each amino acid, ribosomes, messenger RNA, and a number of dissociable protein factors in addition to ATP, GTP, and divalent cations. First the transfer RNAs become charged with amino acids, then the initiation complex is formed. Peptide synthesis does not start until the second aminoacyl tRNA becomes bound to the ribosome. Elongation reactions involve peptide bond formation, dissociation of the discharged tRNA, and translocation. The elongation process is repeated many times until the termination codon is reached. Termination is marked by the dissociation of the messenger RNA... 

In prokaryotic systems, a specific formylating enzyme exists that can recognize tRNAfMet and formylate, its amino terminus utilizing N1 H-formyItetrahydrofolatc as the formyl donor. This reaction serves to ensure that the initiator does not participate in the elongation reactions. For unknown reasons this recognition step is not possessed by eukaryotic systems. 

The elongation reactions begin with the binding of the aminoacyl-tRNA specified by the codon immediately adjacent to the initiator codon. The binding of this aminoacyl-tRNA is catalyzed by an aminoacyl-tRNA binding factor,... 

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