Qiuju Zhou

Stabilizing parallel G-quadruplex DNA by a new class of ligands: Two non-planar alkaloids through interaction in lateral grooves

Human DNA sequences consisting of tandem guanine (G) nucleotides can fold into a four-stranded structure named G-quadruplex via Hoogsteen hydrogen bonding. As the sequences forming G-quadruplex exist in essential regions of eukaryotic chromosomes and are involved in many important biological processes, the study of their biological functions has currently become a hotspot. Compounds selectively binding and stabilizing G-quadruplex structures have the potential to inhibit telomerase activity or alter oncogene expression levels and thus may act as antitumor agents. Most of reported G-quadruplex ligands generally have planar structures which stabilize G-quadruplex by pi-pi stacking. However, based on a pharmacophore-based virtual screening two non-planar G-quadruplex ligands were found. These two ligands exhibit good capability for G-quadruplex stabilization and prefer binding to paralleled G-quadruplex rather than to duplex DNA. The binding of these ligands to G-quadruplex may result from groove binding at a 2:1 stoichiometry. These results have shown that planar structures are not essential for G-quadruplex stabilizers, which may represent a new class of G-quadruplex-targeted agents as potential antitumor drugs.

Verification of specific G-quadruplex structure by using a novel cyanine dye supramolecular assembly: II. The binding characterization with specific intramolecular G-quadruplex and the recognizing mechanism

The supramolecular assembly of a novel cyanine dye, 3,3′-di(3-sulfopropyl)-4,5,4′,5′-dibenzo-9-ethyl-thiacarbocyanine triethylammonium salt (ETC) was designed to verify specific intramolecular G-quadruplexes from duplex and single-strand DNAs. Spectral results have shown that ETC presented two major distinct signatures with specific intramolecular G-quadruplexes in vitro: (i) dramatic changes in the absorption spectra (including disappearance of absorption peak around 660 nm and appearance of independent new peak around 584 nm); (ii) ∼70 times enhancement of fluorescence signal at 600 nm. Furthermore, based on 1H-nuclear magnetic resonance and circular dichroism results, the preferring binding of ETC to specific intramolecular G-quadruplexes probably result from end-stacking, and the loop structure nearby also plays an important role.

Screening Potential Antitumor Agents from Natural Plant Extracts by G-Quadruplex Recognition and NMR Methods

mainlyfocusonscreeningmolecule(s)withknownstructure.However,uptonow,thescreeningofG-quadruplexligands from natural plant extracts, a complicated mixturesystem with multiform unknown chemical frames, has notbeenreported.Herein,weaddressanovelapproachforfastscreeningofG-quadruplex ligands from natural plant extracts. Thisapproach includes the following three steps: judging theexistence of G-quadruplex ligand(s) in the test extracts by

Fast screening and structural elucidation of G-quadruplex ligands from a mixture via G-quadruplex recognition and NMR methods.

Currently, there is a considerable interest in discovering G-quadruplex ligands. Plant-derived agents, because of their diversity in structure and bioactivity and low toxicity, may be a very diverse source of G-quadruplex ligands. However, up to now, the screening of G-quadruplex ligands from natural plant extract has not been reported. Herein, in order to develop a simple method for fast identifying G-quadruplex ligands from plant extract, we intended to substitute the spectral shift in the imino region (delta 10-12) in (1)H NMR spectra of G-quadruplex for in vitro bioassay to judge the existence/nonexistence of G-quadruplex ligand(s) in plant extract, and then couple G-quadruplex recognition with NMR based structure elucidation to identify the structure of the ligand(s) without the need of prior separation. In this paper, we successfully screened a G-quadruplex ligand from a simulated plant extract using this approach. This research work provides a promising tactic to find new leading compounds from nature plant extract.

Controllable assembly and cycling conversion of various supramolecular aggregates of a cyanine dye

Constructing dye supramolecular aggregates and regulating their structures have been very important tasks in recent years due to their excellent properties and promising applications in many fields. In this paper, four kinds of aggregates have been constructed by using a cyanine dye under controllable conditions, and a simple method to realize a cycling conversion around these aggregates has been developed. To construct and regulate these aggregates were easily manipulated and identified, and could be directly observed with unaided eye.

Chiral Transformation of Cyanine Dye Aggregates Induced by Small Peptides

Three small peptides (K4, K5, and K6) with different length were designed to induce the transformation of the assembled state and the chirality of cyanine dye supramolecule. The absorption and circular dichroism (CD) results indicated that, the peptides tend to induce cyanine dye to H-aggregation, competed with Na(+) in PBS, which would induce dye to J-aggregation. Meanwhile, all three peptides could influence the chirality of both J-aggregates induced by Na(+) and H-aggregates, among which K6 could induce chiral reversion of J-aggregates. Furthermore, molecular modeling and energy calculation results have shown that the peptides with different chain length have different conformations. This might be the reason for cyanine dye to form the different chiral assembly induced by these oligo-peptide templates.

Expanding the genetic code for site-specific labelling of tobacco mosaic virus coat protein and building biotin-functionalized virus-like particles

A method for site-specific and high yield modification of tobacco mosaic virus coat protein (TMVCP) utilizing a genetic code expanding technology and copper free cycloaddition reaction has been established, and biotin-functionalized virus-like particles were built by the self-assembly of the protein monomers.

Temperature-sensitive supramolecules self-assembled by G-quadruplex DNA

Using guanine (G)-quadruplexes to construct supramolecular systems receives great attention because G-quadruplexes possess peculiar structural and electronic properties. In this paper, a temperature-sensitive supramolecule self-assembled by G-quadruplexes has been reported, whose structure was demonstrated to be a hexagonal column with rod-shaped G-quadruplex aggregates bundling together.

Polyethylenimine effectively induces, stabilizes, and regulates intramolecular G-quadruplexes.

The interaction between polyethylenimine (PEI) and telomeric DNA was studied. The results demonstrated that PEI could effectively induce, stabilize, and regulate intramolecular G-quadruplexes. The mechanism for these results has been discussed, and was estimated to be condensation effect of PEI.