A Novel Conformationally Constrained Parallel G Quadruplex

Self Cite

The rigid dinuclear [(tap)(2)Ru(tpac)Ru(tap)(2)](4+) complex (1) (TAP=1,4,5,8-tetraazaphenanthrene, TPAC=tetrapyridoacridine) is shown to be much more efficient than the mononuclear bis-TAP complexes at photodamaging oligodeoxyribonucleotides (ODNs) containing guanine (G). This is particularly striking with the G-rich telomeric sequence d(T(2)AG(3))(4). Complex 1, which interacts strongly with the ODNs as determined by surface plasmon resonance (SPR) and emission anisotropy experiments, gives rise under illumination to the formation of covalent adducts with the G units of the ODNs. The yield of photocrosslinking of the two strands of duplexes by 1 is the highest when the G bases of each strand are separated by three to four base pairs. This corresponds with each Ru(tap)(2) moiety of complex 1 forming an adduct with the G base. This separation distance of the G units of a duplex could be determined thanks to the rigidity of complex 1. On the basis of results of gel electrophoresis, mass spectrometry, and molecular modelling, it is suggested that such photocrosslinking can also occur intramolecularly in the human telomeric quadruplex d(T(2)AG(3))(4).

Section: A C H T U N G T R E N N U N G (Phen)]mentioning

confidence: 88%

Section: Instrumentationmentioning

confidence: 99%

A Rigid Dinuclear Ruthenium(II) Complex as an Efficient Photoactive Agent for Bridging Two Guanine Bases of a Duplex or Quadruplex Oligonucleotide

Rickling

Ghisdavu

Pierard

et al. 2010

Self Cite

“…[17] Our strategy is based on the use of a cyclic peptidic scaffold as a topological template for directing the intramolecular assembly of anchored oligonucleotides into a single G-quadruplex topology (Figure 2). It has been conclusively shown that the use of such a peptidic scaffold allows precise control of the parallel-stranded conformation and imparts increased stability to the quadruplex structure.…”

Section: Introductionmentioning

confidence: 99%

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Murat

Bonnet

Heyden

et al. 2010

Self Cite

A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular-like G-quadruplex motif 1 (parallel G-quadruplex conformation), an intramolecular G-quadruplex 2, and a duplex DNA 3 have been designed and developed. The method is based on the concept of template-assembled synthetic G-quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G-quadruplex conformation. Various known G-quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a pi-stacking binding mode showed a higher binding affinity for intermolecular-like G-quadruplexes 1, whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2. In addition, the present method has also provided information about the selectivity of ligands for G-quadruplex DNA over the duplex DNA. A numerical parameter, termed the G-quadruplex binding mode index (G4-BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G-quadruplex 1 against intramolecular G-quadruplex 2. The G-quadruplex binding mode index (G4-BMI) of a ligand is defined as follows: G4-BMI=K(D)(intra)/K(D)(inter), where K(D)(intra) is the dissociation constant for intramolecular G-quadruplex 2 and K(D)(inter) is the dissociation constant for intermolecular G-quadruplex 1. In summary, the present work has demonstrated that the use of parallel-constrained quadruplex topology provides more precise information about the binding modes of ligands.

“…[10] This scaffold has been used recently for the efficient formation of G-quadruplexes. [11] Compounds 3 and 4 have been designed and synthesized by Huisgen 1,3-dipolar cycloaddition (Scheme 1). Interestingly, the resulting triazole linkers are shown to actively participate in the structuring of the G-quartet, as described below.…”

mentioning

confidence: 99%

The Use of a Peptidic Scaffold for the Formation of Stable Guanine Tetrads: Control of a H‐bonded Pattern in Water

Murat

Génnaro

Garcia

et al. 2011

Self Cite