Intramolecular telomerization

In a related reaction, tetraene 26 underwent carbocyclization to give allylic ether 27 [Eq.(26)j [45]. The reaction can be considered as an intramolecular telomerization, and leads to the 1,4-addition of a carbon and an oxygen nucleophile to one of the dienes. The reaction involves a 7r-allyl intermediate, which is subsequendy attacked by the oxygen nucleophile. 

Kim MY et al. (2002) Telomestatin, a potent telomerase inhibitor that interacts quite speciflcally with the human telomeric intramolecular g-quadruplex. J Am Chem Soc 124(10) 2098-2099... 

Ambrus, A., Chen, D., Dai, J., Biabs, T., Jones, R.A. and Yang, D. (2006) Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution, Nucleic Acids Res., 34, 2723-2735. 

Single-molecule FRET has been used to study the kinetics of unfolding of the human telomeric intramolecular G-quadruplex, the DNA-binding orientation of an E.coli REP monomer to a ss/ds DNA junction, four-way... 

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

The 9-anilino proflavine derivative was designed to optimize the interaction with the intramolecular G-quadruplex from human telomere and minimize that with duplex DNA. These compounds have 60 to 100 nM potency in a modified TRAP assay and corresponding low cytotoxicity (93). The triazines have been demonstrated to produce telomere shortening, which is associated with delayed growth arrest and cell senescence (80). The fluoroquinophenoxazines are redesigned topoisomerase II poisons that now interact more specifically with G-quadruplex structures, and this activity is correlated with production of anaphase bridges (78), a property also shared by the cationic porphyrin TMPyP4 (96) and... 

Kim MY, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley LH. 2002. Telomes-tatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular G-quadruplex. J. Am. Chem. Soc. 124 2098-99... 

Dicarborative telomerization has also been successfully applied to intramolecular cyclization reactions. Various tetraenes with enamines, indole, nitroalkanes or carbonyl-stabilized carba-nions give good yields of carbocyclic or heterocyclic five-membered rings, with predominantly the trans arrangement of the two different unsaturated side chains14,15. 

Intramolecular palladium-catalyzed telomerization of diethyl 2,2-bis[( )-2,4-pentadienyl]-propanedioate (4) with diethylamine stereoselectively leads to diethyl fra . -3-(3-diethylamino-l-propenyI)-4-(2-propenyI)-l,l-cycIopentane dicarboxylate (5) in 76% yield with a transicis ratio of >20 11. 

Despite the negative contribution of entropy to stability, most quadruplex structures are stable under physiological conditions. For example, most intramolecular quadruplexes have a AG° <0 at 37°C in a buffer that mimics intracellular conditions (near neutral pH, high concentration, with or without Mg " ). This simply reflects the fact that at physiological temperature the predominant, and sometimes only, species will be the quadruplex structure rather than the single-stranded form. This observation has been well documented for the human telomeric motif. 

The most striking and recent example of structural complexity is the intramolecular human telomeric motif. In sodium, the AG3(T2AG3)3 sequence adopts an intramolecular fold with a central diagonal loop. As a result, each strand has one parallel and one antiparallel neighbour. In potassium, the situation is different. Crystallographic studies indicate that the very same sequence adopts a completely different folding scheme all four DNA strands are parallel, with the three linking trinucleotide loops positioned on the exterior... 

The human telomeric sequence is not the only one forming different intramolecular quadruplexes. The c-myc quadruplex ( Pu27 ) may form at least two... 

The four-repeat human telomeric d[AGGG(TTAGGG)3] sequence was shown to form an intramolecular G-quadruplex in Na solution, in which guanines around each tetrad are syn syn anti anti, loops are successively edgewise-diagonal-edgewise and each G-tract has both a parallel and an antiparallel adjacent strands [Figure lO(a-c)]. By contrast, the crystal structure of the same... 

The four-repeat Tetrahymena telomeric d(T2G4)4 sequence was shown to form an intramolecular G-quadruplex (Figure 11a) with one double-chain-reversal and two edgewise loops. This is the first observation of a double-chain-reversal loop sequence T2 bridges three G-tetrad layers. Furthermore this... 

Figure 10 Structure of intramolecular G-quadruplexes formed by the human telomeric sequence (a-c) in Na solution (d-f) in a -containing crystalf (a, d) Schematic, (b, e) side, and (c,f) top views...

Figure 7 Schematic diagrams of human telomeric quadruplex folding topologies. (A) The fold determined by NMR spectroscopy of the intramolecular G-quadruplex formed by d(AG3(T2AG3)s) in solution with only Na ions. Gray rectangles represent nucleosides with syn glycosidic torsion angles. For clarity, only G-bases are represented. (B) The G-quadruplex fold, with parallel GGG elements and external loops, as determined by X-ray crystallography for the same sequence crystallized in the presence of ions ...

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