A telomerization

A telomerization reaction of isoprene can be carried out by treatment with 2-chloro-3-pentene, prepared by the addition of dry HCl to 1,3-pentadiene (67). An equimolar amount of isoprene in dichi oromethane reacts with the 2-chloro-3-pentene at 10°C with stannic chloride as catalyst. l-Chloro-3,5-dimethyl-2,6-octadiene is obtained in 80% yield by 1,4-addition. 

ITowever, most normal somatic cells lack telomerase. Consequently, upon every cycle of cell division when the cell replicates its DNA, about 50-nucleotide portions are lost from the end of each telomere. Thus, over time, the telomeres of somatic cells in animals become shorter and shorter, eventually leading to chromosome instability and cell death. This phenomenon has led some scientists to espouse a telomere theory of aging that implicates telomere shortening as the principal factor in cell, tissue, and even organism aging. Interestingly, cancer cells appear immortal because they continue to reproduce indefinitely. A survey of 20 different tumor types by Geron Corporation of Menlo Park, California, revealed that all contained telomerase activity. 

Scheme 5-4 Platinum-catalyzed hydrophosphination of acrylonitrile using PH3 (Eq. I) and PH (CH2CH2CN)2 (Eq. 2). The proposed structure of a telomeric by-product of this reaction (I) Is also shown...

Russo, I., A. R. Silver, A. P. Cuthbert, D. K. Griffin, D. A. Trott, and R. F. Newbold. 1998. A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. Oncogene 17(26) 3417-26. 

Acetylation of the histone tails correlates with the activities of genes (Kimura et al., 2005). However, the detailed analyses of the acetylation on the individual lysine residue have revealed that the relationship between the acetylation and the chromatin-compaction is not simple. There are 1-6 lysine residues in each histone subunit, that could be acetylated the Lys of H2A, Lys, Lys, Lys, and Lys ° ofH2B, Lys , Lys , Lys, Lys, Lys, andLys of H3, and Lys, Lys, Lys, and Lys of H4. In mammal, more than ten HATs (7/istone Acetyl Transferases) have been identified, each of which acetylates a specific lysine residue. Acetylation frequently occurs in euchromatin regions, and some in heterochromatin regions. For example, the acetylation of Lys of H4 leads to a telomeric silencing (Kelly et al., 2000). In Drosophila, Lys of H4 is acetylated specifically in the... 

Although not a telomerization, it is mentioned here, that syndiotactic 1,2-polybutadienes were prepared in aqueous emulsions with a 7t-allyl-cobalt catalyst [33]. Similarly, chloroprenes were polymerized using aqueous solutions of [PdCl2(TPPMS)2] and [RhCl(TPPMS)3] as catalysts at 40 °C in the presence of an emulsifier and a chain growth regulator (R-SH, R=Cio-Cis) [35]. Despite the usual low reactivity of chlorinated dienes, these reactions proceeded surprisingly fast, leading to quantitative conversion of 10 g chloroprene in 2 hours with only 50 mg of catalyst (approximate TOP = 3500 h- ). 

Unsaturated tin(IV) derivatives, 2,2-dialkyl-l,3,2-dioxastannoles (348), undergo a telomerization reaction with dialkyltin oxide to give a set of cyclic oligomers (349) <82JOM(224)C37, 83JOM(25l)203>. This telomerization can be combined with the synthesis of 2,2-dialkyl-1,3,2-dioxastannoles (Scheme 35). 

These occur readily between electron-rich alkenes and electron-poor carbonyl compounds. The first example, reported in 1959 (64HC(19-2)729), was the formation of 4,4-diaryloxetane-2,2-dicarbonitriles by the room temperature reaction of 1,1-diarylethylenes and carbonyl cyanide. Continued investigation of this reaction shows that a telomerization product is also formed, the tetraphenylpentadienedinitrile (55) from 1,1-diphenylethylene and carbonyl cyanide. This may be interpreted to indicate that carbon-carbon bond formation may commence somewhat ahead of carbon-oxygen bond formation (75MI51302). This... 

Greider, C. W., and Blackburn, E. H. (1989). A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature337, 331-337. 

The end of a linear chromosome is called a telomere. Telomeres require a special mechanism, because the ends of a linear chromosome can t be replicated by the standard DNA polymerases. Replication requires both a template and a primer at whose 3 end synthesis begins. The primer can t be copied by the polymerase it primes. What copies the DNA complementary to the primer In a circular chromosome, the primer site is to the 3 direction of another polymerase, but in a linear chromosome, no place exists for that polymerase to bind. As a result, unless a special mechanism for copying the ends of chromosomes is used, there will be a progressive loss of information from the end of the linear chromosome. Two characteristics about telomeres help avoid this situation. First, they consist of a short sequence—for example, AGGGTT—repeated many times at the end of each chromosome. Telomeres, therefore, are part of the highly repetitive DNA complement of a eukaryotic cell. Secondly, a specific enzyme, telomerase, carries out the synthesis of this reiterated DNA. Telomerase contains a small RNA subunit that provides the template for the sequence of the telomeric DNA. Eukaryotic somatic cells have a lifespan of only about 50 doublings, unless they are cancerous. One theory holds that a lack of telomerase in cells outside the germ line causes this limitation. 

Addition reactions are also known, both across the polar Sn—O bond and at the metal center. With R2SnO, a telomerization reaction takes place in which the size of the heterocycle can be enlarged in a controlled way [Eq. (55)] (223). Donor ligands, for example, pyridine (Py),... 

More isomeric octyl chlorides than hexyl chlorides were formed by a telomerization reaction involving a second molecule of ethylene. Nuclear magnetic resonance (nmr) suggested that the product was a mixture of about equal weight of primary and secondary chlorides. Since many octyl chloride isomers exist, no conclusion was reached as to the probable structures. 

The versatility of the 2D approach is illustrated with a four-arm starshaped block copolymer (a mixture of 16 components), which was synthesized in our laboratories to understand and demonstrate the advantages of 2D chromatography. These 16 components are a mixture of four different styrene-butadiene (St-Bd) copolymer compositions, each consisting of four molar masses (the St-Bd precursor with one to four arms). Another polymer investigated is a real-world application the deformulation of a telomeric aliphatic polyester. 

All of the following statements concerning telomeres are true except A. Telomeres are tandemly repeated G-rich nucleotide sequences. 

The TRAP (telomeric repeat amplification protocol) assay is a widely used method for detection of telomerase activity. This technique measures the telomerase activity present in cell extracts. Briefly, cellular extract containing telomerase activity is incubated with a telomeric substrate (a short strand of DNA onto which the telomerase wiU. attach the telomeric repeats) followed by polymerase chain reaction (PCR) amplification of the elongated telomere. Detection of the PCR product is by a number of methods, including gel electrophoresis, radiometric detection, ELISA, and real-time PCR detection. ... 

Carbon dioxide has been object of detailed studies either as anion radical scavenger or as direct electrochemical substrate in organic syntheses. Among the dozens of examples of electroorganic syntheses of mono- and dicarboxylic acids even a telomerization of ethylene with C02 has been reported56,57. The reaction has the following stoichiometry ... 

Aqueous, two-phase catalysis is also utilized industrially in a number of other processes apart from hydroformylation. The hydrodimerization of butadiene and water, a telomerization variant yielding 1-octanol or 1,9-nonanediol (cf. Section 6.9), is carried out at a capacity of 5000 tonnes per annum by the Kuraray Corporation in Japan. Rhone-Poulenc is operating two-phase, aqueous, catalytic C—C coupling processes (using TPPTS obtained from Ruhrchemie) for small-scale production of various vitamin precursors such as geranylacetones. Moreover, TPPTS-modified Ru catalysts have been proposed for the homogeneously catalyzed hydrogenation to convert unsaturated ketones into saturated ones. 

Confocal micrographs of yeast cells labeled with a telomere-specific hybridization probe (b) and a fluorescent-labeled antibody specific for SIRS (c). Note that SIRS is localized in the repressed telomeric heterochromatin. Similar experiments with RAR1, SIR2, and SIR4 have shown that these proteins also colocalize with the repressed telomeric heterochromatin. [From M. Gotta et al., 1996,... 

An initiator system has been found independently in the laboratories of Esso and Sun Oil (3, 4). This system promotes transmetalation and chain propagation reactions at comparable rates so that a telomerization reaction of ethylene with aromatic hydrocarbons is realized under relatively mild operating conditions. 

As is characteristic of a telomerization reaction, the product contains a broad molecular-weight range that can be separated into component fractions by distillation. An unusually large amount of intermediate-molecular-weight material results in this case because of the consecutive introduction of several alkyl groups. Under these circumstances the products pyramid. For example, the trialkylbenzene substituted with five-, seven-, and nine-carbon chains may result from any of three intermediates containing one-, five-, and nine-carbon chains or one-, seven-, and nine-carbon chains. 

Although the existence of this enzyme may not be surprising, the mechanism by which it acts is remarkable and unprecedented. Telomerase, like some other enzymes described in this chapter, contains both RNA and protein components. The RNA component is about 150 nucleotides long and contains about 1.5 copies of the appropriate C A, telomere repeat. This region of the RNA acts as a template for synthesis of the T Gy strand of the telomere. Telomerase thereby acts as a cellular reverse transcriptase that provides the active site for RNA-dependent DNA synthesis. Unlike retroviral reverse transcriptases, telomerase copies only a small segment of RNA that it carries within itself. Telomere synthesis requires the 3 end of a chromosome as primer and proceeds in the usual 5 3 direction. Having syn-... 

G-quadruplex ligands induced a telomere dysfunction that is characterized by the appearance of anaphase bridges and telomere end-to-end fusions in treated cells. The induction of short-term apoptosis is also frequently observed. The telomere dysfunction may appear before any evidence of telomere shortening by... 

Telomere length is maintained by telomerase, an enzyme composed of one polypeptide subunit and one RNA subunit. The catalytic subunit of telomerase bears homology to retroviral reverse transcriptases, consistent with its role in catalyzing synthesis of DNA on an RNA template. The 3 end of a telomeric G-rich overhang is the primer for addition of new telomeric sequence, which is templated by the complementary sequence in the telomerase RNA subunit. In vitro, G-rich telomeric sequences readily form G-quadruplexes with distinctive structural features determined by telomere sequence and strand orientation. G4 DNA formation could in principle promote telomere telomere interaction [Figure 4(A)] protect the 3 end from extension or nucleolytic attack [Figure 4(B)] or stabilize t-loops [Figure 4(C)]. 

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