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Over the past decade, nucleic acid chemists have seen the spectacular emergence of molecules designed to interact efficiently and selectively with a peculiar DNA structure named G-quadruplex. Initially derived from classical DNA intercalators, these G-quadruplex ligands progressively became the focal point of new excitement since they appear to inhibit selectively the growth of cancer cells thereby opening interesting perspectives towards the development of novel anti-cancer drugs. The present article aims to help researchers enter this exciting research field, and to highlight recent advances in the design of G-quadruplex ligands. 相似文献
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Gabelica V Baker ES Teulade-Fichou MP De Pauw E Bowers MT 《Journal of the American Chemical Society》2007,129(4):895-904
A promising approach for anticancer strategies is the stabilization of telomeric DNA into a G-quadruplex structure. To explore the intrinsic stabilization of folded G-quadruplexes, we combined electrospray ionization mass spectrometry, ion mobility spectrometry, and molecular modeling studies to study different DNA sequences known to form quadruplexes. Two telomeric DNA sequences of different lengths and two DNA sequences derived from the NHE III1 region of the c-myc oncogene (Pu22 and Pu27) were studied. NH4+ and the ligands PIPER, TMPyP4, and the three quinacridines MMQ1, MMQ3, and BOQ1 were complexed with the DNA sequences to determine their effect on the stability of the G-quadruplexes. Our results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed. Furthermore, the ligands can be classified according to their ability to stabilize the quadruplexes and end stacking is shown to be the dominant mode for ligand attachment. In all cases our solvent-free experimental observations and theoretical modeling reveal structures that are highly relevant to the solution-phase structures. 相似文献
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Conservative methods for the Toda lattice equations 总被引:1,自引:0,他引:1
We are concerned with the numerical integration of the Todalattice equations by using different conservative methods. Numericalexperiments suggest that the global error for isospectral schemesdecreases exponentially with time but it is almost constantfor either symplectic or more general integrators. We providea theoretical explanation for these experimental findings. 相似文献
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Allain C Monchaud D Teulade-Fichou MP 《Journal of the American Chemical Society》2006,128(36):11890-11893
G-quadruplex represents a suitable scaffold for FRET (fluorescence resonance energy transfer) since its two external quartets offer two well-defined binding sites for concomitant trapping of donor/acceptor partners. Combining selective G-quadruplex binders (macrocyclic bis(quinacridine) BOQ(1) or monomeric quinacridine MMQ(1), donor) with a highly fluorescent DNA probe (thiazole orange, acceptor), we designed a structure-specific FRET-system based on an unprecedented noncovalent ternary complex. This system could be potentially usable as a signature for quadruplex-DNA conformation in solution, but also might offer a unique means for observing cation and ligand binding influence on quadruplex topology. 相似文献