Isoleucine analogs

Figure 1 Structures of the isoleucine analogs used in this study...

Table 1 Incorporation of isoleucine analogs into DHFR...

Further Treiber and Iaccarino(25) studying isoleu-cyl-tENA synthetases partially purified from wild type E.coli and from an isoleucine requiring mutant showed that thiaisoleucine and another isoleucine analog,... 

Figure 30-19. The analogous first three reactions in the catabolism of leucine, valine, and isoleucine. Note also the analogy of reactions and to reactions of the catabolism of fatty acids (see Figure 22-3). The analogy to fatty acid catabolism continues, as shown in subsequent figures.

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

A concise and efficient asymmetric synthesis of L-( + )-carbafuranomycin 452, a novel analog of L-( + )-furanomycin, which is an unusual antibiotic amino acid of great interest, due to its activity as an isoleucine antagonist, has been reported (496). The synthesis starts with the 1,3-dipolar cycloaddition of a chiral nitrile oxide (obtained in situ from hydroximinoyl chloride 453 via slow addition of NEt3) with cyclopentadiene. Then methylation of cyclopentenyl acetate 454,... 

Such a rearrangement is not observed with glycine, alanine, 2-aminobutanoic acid or 2-amino-3-cyclohexylpropanoic acid, occurs partially with valine and isoleucine, but is complete with phenylalanine, tyrosine and threonine. By analogy with previous dediazoniation studies on 2-amino acids in acidic media,309 this rearrangement has been explained by the anchimeric assistance of alkyl (Val, lie), aryl (f he, Tyr) or hydroxy (Thr) groups during the dediazoniation process 306 for example, in the case of phenylalanine (4). 

Compare the outer surface of of the standard polypeptide and its retro-inverso analog. How would your answer be affected by the presence of threonine or isoleucine in the peptides ... 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

In the degradation of isoleucine, (3 oxidation proceeds to completion in the normal way with generation of acetyl-CoA and propionyl-CoA. However, in the catabolism of leucine after the initial dehydrogenation in the (3-oxidation sequence, carbon dioxide is added using a biotin enzyme (Chapter 14). The double bond conjugated with the carbonyl of the thioester makes this carboxylation analogous to a standard (3-carboxylation reaction. Why add the extra C02 ... 

Figure 13.4 The double sieve analogy for the editing mechanism of the isoleucyl-tRNA synthetase. The active site for the formation of the aminoacyl adenylate can exclude amino acids that are larger than isoleucine but not those that are smaller. On the other hand, a hydrolytic site that is just large enough to bind valine can exclude isoleucine while accepting valine and all the smaller amino acids. (In some enzymes, the hydrolytic site offers specific chemical interactions that enable it to bind isosteres of the correct amino acid as well as smaller amino acids.)...

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