Qianfan Yang

A dye with a large aromatic substituent (AB-P4) presented higher selectivity for specific G-quadruplexes than those of small ones (B-P4 and TC-P4).

The recognizing ability of parallel c-myc G-quadruplex by dimeric cyanine dyes depends on their linker length.

Using cyanine dyes supramolecular as molecular probes to mark FA has important significance in life sciences and pharmaceutical chemistry, which can detect FA as drug efficacy mechanism and the change in physiological activity. In the present paper, we investigated supramolecular assembly and chiral inducement of cyanine dyes template by FA with absorption and circular dichroism (CD) spectra. The result suggests that FA can induce cyanine dyes from J-aggregation to monomer along with different colors change and has strong affinity with cyanine dye monomer. The template of FA not only can translate the chirality of MTC H-aggregation to other two states, but also induce ETC J-aggregation to molecular rearrangement and form left-handed helix of J-aggregates. Besides, the association of PTC with FA, i. e. binding to FA gave rise to the J-aggregation CD signals. Meanwhile, it was inferred that the meso substituent of cyanine dyes play an important role in the interaction between FA and the J-aggregation: the smaller the meso substituent, the higher the affinity interacted with FA. Clearly, the binding abilities between cyanine dyes and FA follow the order of MTC>ETC>PTC. These results support that the cyanine dyes supramolecular aggregates can be used as a kind of excellent molecular probes for specific recognition of FA and achieve the effect of visual inspection.

The polo-like kinase 1 (Plk1) is a critical regulator of cell division that is overexpressed in many types of tumors. Thus, a strategy in the treatment of cancer has been to target the kinase activity (ATPase domain) or substrate-binding domain (Polo-box Domain, PBD) of Plk1. However, only few synthetic small molecules have been identified that target the Plk1-PBD. Here, we have applied an integrative approach that combines pharmacophore modeling, molecular docking, virtual screening, and in vitro testing to discover novel Plk1-PBD inhibitors. Nine Plk1-PBD crystal structures were used to generate structure-based hypotheses. A common pharmacophore model (Hypo1) composed of five chemical features was selected from the 9 structure-based hypotheses and used for virtual screening of a drug-like database consisting of 159,757 compounds to identify novel Plk1-PBD inhibitors. The virtual screening technique revealed 9,327 compounds with a maximum fit value of 3 or greater, which were selected and subjected to molecular docking analyses. This approach yielded 93 compounds that made good interactions with critical residues within the Plk1-PBD active site. The testing of these 93 compounds in vitro for their ability to inhibit the Plk1-PBD, showed that many of these compounds had Plk1-PBD inhibitory activity and that compound Chemistry_28272 was the most potent Plk1-PBD inhibitor. Thus Chemistry_28272 and the other top compounds are novel Plk1-PBD inhibitors and could be used for the development of cancer therapeutics.

A G-quadruplex is identified which can exhibit two different motifs, respectively, corresponding to Na⁺ and K⁺. The relative amount of each motif is related to the Na⁺/K⁺ ratio. Based on selective recognition of the G-quadruplex motifs by a cyanine dye aggregate, a method for both colorimetric and quantitative measurements of Na⁺/K⁺ ratios is constructed.

Biomolecules are promising templates that play important roles in controlling the supramolecular assembly process more flexibly and precisely due to their unique characteristic structures. Here we first present a G-quadruplex with a chair-like antiparallel motif as a novel dual-functional regulation template in the aggregation of a cyanine dye.

G-quadruplexes have attracted growing attention as a potential cancer-associated target for both treatment and detection in recent years. For detection purpose, high specificity is one of the most important factors to be considered in G-quadruplex probe design. It is well known that end stacking and groove binding are two dominated quadruplex-ligand binding modes, and currently most reported G-quadruplex probes are designed based on the former, which has been proven to show good selectivity between quadruplexes and non-quadruplexes. Because groove of G-quadruplex also has some unique chemical properties, it could be inferred that probes that can interact with both the groove and G-tetrad site of certain G-quadruplexes simultaneously might possess higher specificity in aspects of discriminating different quadruplexes. In this article, we report a cyanine dye as a potential novel probe scaffold that could occupy both the 5′-end external G-tetrad and the corresponding groove of the G-quadruplex simultaneously. By using various spectrum and nuclear magnetic resonance techniques, we give a detailed binding characterization for this dual-site simultaneous binding mode. A preliminary result suggests that this mode might provide highly specific recognition to a parallel-stranded G-quadruplex. These findings and the structural elucidation might give some clues in aspects of developing highly specific G-quadruplex probes.

Copper(II) (1_CuCu–21_CuCu) and previously established experimental anticancer platinum(II) metallointercalator complexes (1_PtPt–16_PtPt) have been prepared and investigated for their antimicrobial properties. These complexes are of the general structure [M(I_L)(A_L)]²⁺ where I_L represents functionalised 1,10-phenanthrolines (1_ILIL–10_ILIL), and A_L represents 1,2-diaminoethane, 1S,2S- or 1R,2R-diaminocyclohexane. The structures of synthesised complexes were confirmed using a combination of elemental analysis, UV spectrometry, circular dichroism, ¹H and [¹H–¹⁹⁵Pt]-HMQC NMR, X-ray crystallography, and electrospray ionisation mass spectrometry and where appropriate. Crystallisation attempts yielded single crystals of [Cu(4-methyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)](ClO₄)₂ (4_CuCu), [Cu(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)(H₂O)](ClO₄)₂·1.5H₂O (10_CuCu) and [Cu(5,6-dimethyl-1,10-phenanthroline)₃](ClO₄)₂·5,6-dimethyl-1,10-phenanthroline·2H₂O (21_CuCu). Growth inhibition of liquid cultures of bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), and yeast (Saccharomyces cerevisiae) discerned the most antimicrobially potent metal complexes ≤20 μM, as well as that of their intercalating ligands alone. To further investigate their mode of antimicrobial activity, membrane permeabilisation caused by selected complexes was visualised by means of a cell viability kit under fluorescence microscopy.