G-quadruplexes

Guyen B et al. (2004) Synthesis and evaluation of analogues of 10H-indolo[3,2-b] quinoline as G-quadruplex stabilising ligands and potential inhibitors of the enzyme telomerase. Org Biomol Chem 2(7) 981-988... 

Riou JF et al. (2002) Cell senescence and telomere shortening induced by a new series of speciflc G-quadruplex DNA ligands. Proc Natl Acad Sci USA 99(5) 2672-2677... 

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... 

Read M et al. (2001) Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc Natl Acad Sci USA 98(9) 4844-4849... 

Haider SM, Parkinson GN, Neidle S (2003) Structime of a G-quadruplex-ligand complex. J Mol Biol 326(1) 117-125... 

Fedoroff OY et al. (1998) NMR-based model of a telomerase-inhibiting compoimd bound to G-quadruplex DNA. Biochemistry 37(36) 12367-12374... 

Fig. 10.12 (A) The cation-templated hierarchic self-assembly of guanine alkoxysilane gives the C-quartet and (B) the G-quadruplex transcribed in solid hybrid materials by the sol-gel process.

Figure 10.13 shows the first picture of the dynamic G-quadruplex transcribed at the nanometric level it unlocks the door to a new materials world paralleling that of biology. 

Kaucher, M.S., Harrell, W.A. and Davis, J.T. (2006) A unimolecular G-quadruplex that functions as a synthetic transmembrane Na+ transporter. Journal of the American Chemical Society, 128,... 

Ca2+aq reacts very rapidly with adp3- and with atp4-(236,710). Rate constants for onward reaction of [M(adp)] and [M(atp)]2, M — Ca2+, Mg24, or Mn2+, with creatine phosphotransferase are similar - 1. 7 x 106, 5.3 x 106, 7.4 x l(r M 4s 1 respectively (at 284 K) for the adp complexes, and indeed are similar to the value of 23 x 106M-1s-1 for the reaction of adp itself with creatine phosphotransferase (711). Kinetic parameters and binding constants have been established for interaction of the antiparallel form of the G-quadruplex d(T4G4T4) with Ca2+aq and for the subsequent Ca2+-promoted antiparallel parallel equilibrium (cf. Section IV.C above) (607). 

Figure 9.11 G-quadruplex DNA. (From Wozki and Schmidt, 2002. Reproduced with permission from John Wiley Sons., Inc.)...

Figure 9.12 Schematic diagram of interconversions between the Na+ and K+ forms of telomeric G-quadruplexes. (Reproduced from Ambrus et al., 2006, by permission of Oxford University Press.)...

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. 

Apart from telomeres, G-quadruplexes are also present in the upstream promoter regions of certain oncogenes. G-quadruplex targeted molecules may interact at these sites as well. In fact, the cationic prophyrin, TMPyP4 and the core modified expanded prophyrin analogue 5,10,15,20-[tetra(N-methyl-3-pyridyl)]-26,28-diselenasapphyrin chloride (Se2SAP) have been found to cause repression of transcriptional activation of c-MYC in cells by G-quadruplex stabilization (Seenisamy et al, 2005). 

Han H, Cliff CL, Hurley LH (1999) Accelerated assembly of G-quadruplex structures by a small molecule. Biochemistry 38 6981-6986... 

Lee YJ, Park SJ, Ciccone SL, Kim CR, Lee SH (2006) An in vivo analysis of MMC-induced DNA damage and its repair. Carcinogenesis 27(3) 446-453 Loehrer PJ, Einhom LH (1984) Drugs five years later. Cisplatin. Ann Intern Med 100(5) 704-713 Li G, Widom J (2004) Nucleosomes facilitate their own invasion. Nat Struct Mol Biol 11 763-769 Liu W, Sun D, Hurley LH (2005) Binding of G-quadruplex interactive agents to distinct G-quadruplexes induces different biological effects in MiaPaca cells. Nucleosides Nucleotides Nucleic Acids 24(10-12) 1801-1815... 

Seenisamy J, Bashyam S, Gokhale V, Vankayalapati H, Sun D, Siddiqui-Jain A, Streiner N, Shin-Ya K, White E, Wilson WD, Hurley EH (2005) Design and synthesis of an expanded porphyrin that has selectivity for the c-MYC G-quadruplex structure. J Am Chem Soc 127(9) 2944-2959 Sen D, Crothers DM (1986) Influence of DNA-binding drugs on chromatin condensation. Biochemistry 25(7) 1503-1509... 

Sun D, Thompson B, Gathers BE, Salazar M, Kerwin SM, Trent JO, Jenkins TC, Neidle S, Hurley LH (1997) Inhibition of human telomerase by a G-quadruplex-interactive compound. J Med Chem 40 2113-2116... 

Davis, J. T. Lipophilic G-quadruplexes are self-assembled ion pair receptors, and the bound anion modulates the kinetic stability of these complexes. J Am Chem Soc 2003, 125, 10830-10841. 

Figure 3.5 Disulfide-based dynamic combinatorial library selects for peptidic tiomodi-sulfide P-P and acridone-peptide heterodisulfide A-P G-quadruplex DNA ligands.

This relatively small DCL yielded the first peptidic ligand for G-quadruplex DNA, providing a lead compound for the further development of novel G-quadruplex ligands with possible therapeutic utility. 

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