Reversible chain elongation

Model for Reversible Chain Elongation (Linear Growth)... 

Folmer-Andersen JF, Lehn J-M (2011) Thermoresponsive dynamers thermally induced, reversible chain elongation of amphiphilic poly(acylhydrazones). J Am Chem Soc 133 10966-10973... 

Acetogenins. Acetogenins are produced upon chain elongation with activated acetate units (or malonate followed by loss of carbon dioxide). A simplified sketch of this sequence is given in Fig. 1. During the first steps, a Claisen-type condensation of two acyl precursors yields a (3-ketoacyl intermediate A. Upon reduction to B and dehydration to C, followed by hydrogenation to D and hydrolysis, the chain elongated fatty acid E is produced. The next cycle will add another two carbons to the chain. Similarly, a reversed sequence leads to chain... 

In general, the behavior of all classes of polymer behavior is Hookean before the yield point. The reversible recoverable elongation before the yield point, called the elastic range, is primarily the result of bending and stretching of covalent bonds in the polymer backbone. This useful portion of the stress-strain curve may also include some recoverable uncoiling of polymer chains. Irreversible slippage of polymer chains is the predominant mechanism after the yield point. 

Didanosine (dideoxyinosine, ddl) is a nucleoside analog sometimes used to treat HIV infections. This drug is converted metabolically to 2,3 -dideoxyATP (ddATP), which blocks DNA chain elongation when it is incorporated into viral DNA synthesized by reverse transcriptase. Why does DNA synthesis stop ... 

Acetyl-CoA is most often the primer or starter piece for fatty acid synthesis, but butyryl-CoA is a better primer for rabbits. Butyryl-CoA arises from acetyl-CoA by a reversal of (3 oxidation, the necessary enzymes occurring in significant amounts in the cytosol.79 If either acetyl-CoA or butyryl-CoA is the starter piece, chain elongation via malonyl-CoA (Fig. 18-12) leads to fatty acids with an even number of carbon... 

Didanosine is a synthetic purine nucleoside analog that inhibits the activity of reverse transcriptase in HIV-1, HIV-2, other retroviruses and zidovudine-resistant strains. A nucleobase carrier helps transport it into the cell where it needs to be phosphorylated by 5 -nucleoiidase and inosine 5 -monophosphate phosphotransferase to didanosine S -monophosphate. Adenylosuccinate synthetase and adenylosuccinate lyase then convert didanosine 5 -monophosphate to dideoxyadenosine S -monophosphate, followed by its conversion to diphosphate by adenylate kinase and phosphoribosyl pyrophosphate synthetase, which is then phosphorylated by creatine kinase and phosphoribosyl pyrophosphate synthetase to dideoxyadenosine S -triphosphate, the active reverse transcriptase inhibitor. Dideoxyadenosine triphosphate inhibits the activity of HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate, and its incorporation into viral DNA causes termination of viral DNA chain elongation. It is 10-100-fold less potent than zidovudine in its antiviral activity, but is more active than zidovudine in nondividing and quiescent cells. At clinically relevant doses, it is not toxic to hematopoietic precursor cells or lymphocytes, and the resistance to the drug results from site-directed mutagenesis at codons 65 and 74 of viral reverse transcriptase. 

Palmitate can serve as a precursor for both longer and unsaturated fatty adds. Chain elongation takes place in both the endoplasmic reticulum and mitochondria. In the latter, this is a simple reversal of the /3-oxidation reaction sequence, except that the step that would normally require FADH2 requires NADPH instead. This system is designed for the elongation of short-chain acids. There is no activity with palmitate. 

One solid-phase synthesis of amylin has been reported in 1991 by Balasubramaniam et al. (81). Standard A -Boc chemistry was used for the synthesis, and MBHA resin was selected as the solid support. The coupling was done by using the symmetric anhydride method except for Arg, Asn, and Gin, which were coupled as their HOBt esters (refer to the section on Corticotropin-releasing factor synthesis for details). After completing the chain elongation, the peptide was cleaved from the resin using HF at 0 °C. The residue was then oxidized with K3Fe(CN)e to form the disulfide bond, followed by purihcation on semipreparative reversed phase column. The overall yield of the synthesis was between 10-20%. 

The right start. Suppose that you want to assay reverse transcriptase activity. If polyriboadenylate is the template in the assay, what should you use as the primer Which radioactive nucleotide should you use to follow chain elongation ... 

Mitochondrial elongation occurs by successive addition and reduction of acetyl units in a reversal of fatty acid oxidation. Although fatty acid P-oxidation and mitochondrial chain elongation have the same organelle location, reversal of a tra/ii-2-enoyl-CoA reductase P-oxidation is not feasible the FAD-dependent acyl-CoA dehydrogenase of P-oxidation is substituted by a more thermodynamically favorable enzyme reaction, catalyzed by NADPH-dependent enoyl-CoA reductase, to produce overall negative free-energy for the sequence. Enoyl-CoA reductase firom liver mitochondria is distinct from... 

Reverse Transcriptase - 3 -Azido-2 3 -dideoxythymidine (AZT), when converted to the corresonding 5 triphosphate in cells, is an inhibitor of the HIV reverse transcriptase enzyme, which is responsible for making viral DNA from viral RNA. Other nucleoside analogs, such as 2 3 -dideoxycytidine (ddC), 2 3 -dideoxyinosine (ddl), and 2 3 -didehydro-3 -deoxythymidine (d4T) (see here) are also converted to triphosphates and act by blocking DNA chain elongation after they are incorporated into DNA. 

MECHANISM OF ACTION AND BACTERIAL RESISTANCE Rifampin forms a stable complex with DNA dependent RNA polymerase, leading to suppression of initiation of chain formation (but not chain elongation) in RNA synthesis. High concentrations of rifampin can inhibit RNA synthesis in mammahan mitochondria, viral DNA-dependent RNA polymerases, and reverse transcriptases. Rifampin is bactericidal for both intracellular and extracellular microorganisms. 

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