Targeting Oncogene Promoters and Ribosomal RNA Biogenesis by G-Quadruplex Binding Ligands Translate to Anticancer Activity.

G-Quadruplex (GQ) nucleic acids are promising therapeutic targets in anticancer research due to their structural robustness, polymorphism, and gene-regulatory functions. Here, we presented the structure-activity relationship of carbazole-based monocyanine ligands using region-specific functionalization with benzothiazole (TCA and TCZ), lepidine (LCA and LCZ), and quinaldine (QCA and QCZ) acceptor moieties and evaluated their binding profiles with different oncogenic GQs. Their differential turn-on fluorescence emission upon GQ binding confirmed the GQ-to-duplex selectivity of all carbazole ligands, while the isothermal titration calorimetry results showed selective interactions of TCZ and TCA to and GQs, respectively.

Metal catalyst-free photo-induced alkyl C-O bond borylation.

Metal catalyst free, blue visible light-induced C-O bond borylation of unactivated tertiary alkyl methyl oxalates has been developed to furnish tertiary alkyl boronates. From the secondary alcohols activated with imidazolylthionyl, moderate yields of boronates were attained under standard photo-induced conditions. Preliminary mechanistic studies confirmed the involvement of a (DMF)2-B2cat2 adduct that weakly absorbs light at 437 nm so as to initiate a Bcat radical.

Stabilization of an abasic site paired against an unnatural triazolyl nitrobenzene nucleoside.

An abasic site is the most frequently observed among the various forms of DNA lesions in genomic DNA. If left unrepaired, an abasic site might turn out to be a principle cause for deleterious mutations and can be threat to cellular survival. Thus, to keep cellular integrity and measure the extent of DNA damage, recognition and stabilization of the abasic sites (apurinic/apyrimidinic site = Ap) are essential.

Excitonically Coupled Cyclic BF Arrays of Calix[8]- and Calix[16]phyrin as Near-IR-Chromophores.

Two giant calix[n]phyrin derivatives namely calix[8]- (4) and calix[16]phyrin (5), involving two and four BF units, respectively, were prepared through the condensation of the bis-naphthobipyrrolylmethene-BF complex (3) with pentafluorobenzaldehyde. Calix[n]phyrins 4 and 5 display extremely high extinction coefficients (3.67 and 4.

Tetrazolylpyrene unnatural nucleoside as a human telomeric multimeric G-quadruplex selective switch-on fluorescent sensor.

We report herein the specific sensing of dimeric H45 G-quadruplex DNA via a fluorescence light-up response using fluorescent tetrazolylpyrene nucleoside (B) as a probe. The strong binding of the probe via an intercalative stacking interaction inside the connecting loop of two G-quadruplex units of H45 and the discrimination to other monomeric and long DNA duplexes are accompanied by a drastic enhancement of the emission intensity without compromising the conformation and stability.

Trifunctional fluorescent unnatural nucleoside: Label free detection of T-T/C-C base mismatches, abasic site and bulge DNA.

The detection and targeting of both the mismatched and abasic DNA is highly important which would ultimately help in designing new diagnostics and chemotherapeutics. Furthermore, sensing and targeting the bulge sequence with a fluorescent probe would be useful to study the role of bulges in nucleic acid function or could have significant therapeutic potential. Thus, detection of specific bulges by small fluorescent molecules is an attractive research area since the past several years.

Donor/acceptor chromophores-decorated triazolyl unnatural nucleosides: synthesis, photophysical properties and study of interaction with BSA.

Much effort has been put forth to develop unnatural, stable, hydrophobic base pairs with orthogonal recognition properties and study their effect on DNA duplex stabilisation. Our continuous efforts on the design of fluorescent unnatural biomolecular building blocks lead us to the synthesis of some triazolyl donor/acceptor unnatural nucleosides via an azide-alkyne 1,3-dipolar cycloaddition reaction as a key step, which we want to report herein. We have studied their photophysical properties and found interesting solvatochromic fluorescence for two of the nucleosides.

Regioselective and stereoselective route to N2-β-tetrazolyl unnatural nucleosides via SN2 reaction at the anomeric center of Hoffer's chlorosugar.

We are reporting a regioselective and stereoselective route to N2-β-tetrazolyl aromatic donor/acceptor unnatural nucleosides as new class of possible DNA base analogs. The SN2 substitution reaction at the anomeric center of Hoffer's chlorosugar with various 5-substituted aromatic tetrazoles in THF in presence of K2CO3 proceeds with regioselectivity at N2-tetrazoles and stereoselectivity at α-chlorosugar with very good yield. The stereoelectronic and steric effects play a crucial role for the observed outcome which is also supported from a theoretical (DFT) study.

Expression of the ZNT1 Zinc Transporter from the Metal Hyperaccumulator Noccaea caerulescens Confers Enhanced Zinc and Cadmium Tolerance and Accumulation to Arabidopsis thaliana.

Prompt regulation of transition metal transporters is crucial for plant zinc homeostasis. NcZNT1 is one of such transporters, found in the metal hyperaccumulator Brassicaceae species Noccaea caerulescens. It is orthologous to AtZIP4 from Arabidopsis thaliana, an important actor in Zn homeostasis.

Design and synthesis of triazolyl-donor/acceptor unnatural nucleosides and oligonucleotide probes containing triazolyl-phenanthrene nucleoside.

In the context of abasic DNA or DNA duplex stabilization, several unnatural nucleosidic/non-nucleosidic base surrogates have been reported. Toward this end, we have designed and synthesized triazolyl-aromatic donor chomophores as unnatural nucleoside analogs. These modifications display markedly higher thermal stabilization of abasic DNA duplex in comparison to the stabilization offered by other nucleoside/non-nucleoside base surrogates reported in the literature.

Triazolyl donor/acceptor chromophore decorated unnatural nucleosides and oligonucleotides with duplex stability comparable to that of a natural adenine/thymine pair.

We report the design and synthesis of triazolyl donor/acceptor unnatural nucleosides via click chemistry and studies on the duplex stabilization of DNA containing two such new nucleosides. The observed duplex stabilization among the self-pair/heteropair has been found to be comparable to that of a natural A/T pair. Our observations on the comparable duplex stabilization has been explained on the basis of possible π-π stacking and/or charge transfer interactions between the pairing partners.

Bioinformatic approaches for identification and characterization of olfactomedin related genes with a potential role in pathogenesis of ocular disorders.

Purpose: To identify olfactomedin domain containing proteins, which are expressed in the eye and have similarity to myocilin, to test as potential candidates for eye diseases. Most of the mutations in myocilin causing primary open angle glaucoma are located in the olfactomedin domain. In vitro experiments demonstrated interaction between optimedin and myocilin through the conserved olfactomedin domains of the proteins in rats, and it was speculated that optimedin might have a role in the pathogenesis of ocular disorders.