Nanomechanics of G-quadruplexes within the promoter of the KIT oncogene

G-quadruplexes (G4s) are tetrahelical DNA structures stabilized by four guanines paired via Hoogsteen hydrogen bonds into quartets. While their presence within eukaryotic DNA is known to play a key role in regulatory processes, their functional mechanisms are still under investigation. In the present work, we analysed the nanomechanical properties of three G4s present within the promoter of the KIT proto-oncogene from a single-molecule point of view through the use of magnetic tweezers (MTs). The study of DNA extension fluctuations under negative supercoiling allowed us to identify a characteristic fingerprint of G4 folding. We further analysed the energetic contribution of G4 to the double-strand denaturation process in the presence of negative supercoiling, and we observed a reduction in the energy required for strands separation.     

Competitive inhibition of Cu, Zn superoxide dismutase by monovalent anions.

Polarographic measurements showed that N₃^? and halides $\text{in}$ hibit the activity of bovine Cu, Zn superoxide dismutase in a competitive fashion, as previously demonstrated for CN^? and OH^?. All anions increase the spin-lattice nuclear magnetic relaxation time (T₁) of aqueous solutions of the enzyme as well, but the stability constants measured from T₁ data are lower than those calculated from activity data. The results suggest that substrate and anionic inhibitors bind during the catalytic action at the water coordination position of the enzyme copper, and that these inhibitors may have a greater affinity for the cuprous form of the enzyme which is generated in the catalytic cycle.     

A new method for extracting conodonts and radiolarians from chert with NaOH solution

Microfossils are important components of sedimentary rocks used for palaeontological, biostratigraphic, palaeoenvironmental and palaeoclimatic investigations. They are usually extracted from rocks using an acid solution, which might vary depending on the embedding rock lithology. Here we propose a new method using common NaOH (sodium hydroxide; soda) to digest cherts (micro- and cryptocrystalline quartz) instead of the standard technique based on HF (hydrofluoric acid). This new method allows the collection of undamaged specimens of different kinds of microfossils, such as conodonts, radiolarians, teeth and dermal scales, the minerology of which is still preserved (e.g. biogenic apatite in conodonts). The use of soda is thus recommended, as it is less dangerous, less expensive, and it better preserves the extracted microfossils both in shape and mineralogy.     

New substance P receptor antagonists. Conception, synthesis and biological evaluation of spirolactam derivatives and their tripeptide Cbz-Pro-Leu-Trp-OBzl(CF3)2 and lactam pseudopeptide derivatives

New chemical entities were designed from the C-terminal sequence of GR71251, an NK₁ pseudopeptide antagonist. Three new NK₁ antagonists were identified with high affinity and selectivity for NK₁ receptors.