Fluorescence Light-Up of G4 DNA Structures Using Azlactone-Based Probes.

G-rich sequences of DNA and RNA can form G-quadruplex (G4) structures, modulating a myriad of biological processes. Thus, it is imperative to understand the structural topologies, location, and function of G4s under cell-free conditions and in the cellular milieu. In the present study, we report three small-molecule fluorescent probes based on azlactones (-) that significantly light up (∼65-135-fold) the parallel topology of the , , and mitochondrial HRCC G4 DNAs.

Natural product-mediated reaction hijacking mechanism validates Plasmodium aspartyl-tRNA synthetase as an antimalarial drug target.

Malaria poses an enormous threat to human health. With ever-increasing resistance to currently deployed antimalarials, new targets and starting point compounds with novel mechanisms of action need to be identified. Here, we explore the antimalarial activity of the Streptomyces sp natural product, 5'-O-sulfamoyl-2-chloroadenosine (dealanylascamycin, DACM) and compare it with the synthetic adenosine monophosphate (AMP) mimic, 5-O-sulfamoyladenosine (AMS).

Synthesis of -dA Damaged DNAs to Probe the Replication Ability of Human Translesion Polymerases.

The DNA adducts formed by the alkenylbenzene natural products, safrole (SF) and methyleugenol (MEG) are primarily attributed to their reported carcinogenic properties. Herein, we report a concise strategy to access -Ac-SF/MEG-dA phosphoramidites, which were selectively incorporated into DNA oligonucleotides by solid-phase DNA synthesis. The replication studies using human polymerases hpolκ and hpolη showed that both polymerases replicate these adducts error-free, which indicates that these polymerases do not contribute to the adduct-induced mutagenicity.

Structural elucidation of HIV-1 G-quadruplexes in a cellular environment and their ligand binding using responsive F-labeled nucleoside probes.

Understanding the structure and recognition of highly conserved regulatory segments of the integrated viral DNA genome that forms unique topologies can greatly aid in devising novel therapeutic strategies to counter chronic infections. In this study, we configured a probe system using highly environment-sensitive nucleoside analogs, 5-fluoro-2'-deoxyuridine (FdU) and 5-fluorobenzofuran-2'-deoxyuridine (FBFdU), to investigate the structural polymorphism of HIV-1 long terminal repeat (LTR) G-quadruplexes (GQs) by fluorescence and F NMR. FdU and FBFdU, serving as hairpin and GQ sensors, produced distinct spectral signatures for different GQ topologies adopted by LTR G-rich oligonucleotides.