Quadruplex DNA-guided ligand selection from dynamic combinatorial libraries of acylhydrazones

Abstract

Synthesis of dynamic combinatorial libraries of acylhydrazones in the presence of a G-quadruplex DNA template, followed by pull-down with streptavidin-coated magnetic beads, allows the identification of putative G-quadruplex binders.

Mass Spectrometry of Nucleic Acid Noncovalent Complexes

“…Phen-DC3, 360A, and some analogues have such a strong preference for 2-quartet (1-K + ) antiparallel G-quadruplexes that they can induce a rearrangement from 3-quartets (2-K + ) human telomeric sequences to a 2-quartets topology. A conformational selection mechanism was proposed .…”

Optimization of G‐Quadruplex Ligands through a SAR Study Combining Parallel Synthesis and Screening of Cationic Bis(acylhydrazones)

“…Fluorescence titrations : Isothermal fluorescence titrations were performed as described elsewhere [49,73] . 5′‐Cy5‐labeled oligonucleotides were dissolved at a concentration of 1 μM in K100 buffer (Table S3), annealed at 95 °C for 5 min, slowly cooled to room temperature, and then further diluted with the titration buffer (10 mM LiAsO 2 Me 2 , 100 mM KCl, 0.5 w / v % CHAPS, 0.05 v / v % Triton X‐100, pH 7.2) to a final concentration of 2.22 nM.…”

“…Correlation analysis of the total number of aromatic rings (NAr) and ligandinduced stabilization effect (∆Tm) for 90 ligands and four G4 structures S9 formyl-1-ethylquinolinium iodide (1g) and 6-formyl-1-benzylquinolinium iodide (2h) were prepared as previously described. [1,2] The synthesis of 2d, 2e and 2i is described below.…”

“…More recently, PhenDH2 was shown to bind to G4‐RNA structures in LANA1 mRNA of Kaposi's sarcoma‐associated herpesvirus and interfere with nuclear export, nucleolin binding, and translation of this mRNA more efficiently than PhenDC3 [48] . With the aim of further exploration of this promising scaffold, we elaborated the generation of G4‐targeted dynamic combinatorial libraries (DCLs) of bis(acylhydrazones) in conditions compatible with native G4‐DNA structures [49] . However, the identification of ligands from DCLs turned out to be tedious and not free of bias due to nonspecific interactions of ligands with the oligonucleotide support (i. e., streptavidin‐coated magnetic beads).…”

Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives

“…Acylhydrazone is formed by the condensation of hydrazine and an aldehyde or ketone, containing both oxygen and nitrogen atoms that are involved in the formation of hydrogen bonds in living organisms and increase the affinity between receptors, thereby, inhibiting numerous physiological and chemical processes in vivo [ 1 , 2 , 3 , 4 , 5 ]. Acylhydrazone compounds are special in terms of both their structure and properties and have been the focus of considerable research by chemists.…”