Global features of intermediate mass fragment cross sections in Ne induced interactions

Inclusive cross sections of intermediate mass fragments (6Z16) have been measured in ²⁰Ne induced reactions on silver and gold targets at 20, 30, 40, 50 and 60 MeV/u incident energies. Whereas the production yields remain approximately constant for the Ne+Ag system, they increase by a factor of two for the Ne+Au system over the same bombarding energy range. These results are discussed in the framework of two fragmentation models.     

YOYO as a Dye to Track Penetration of LK15 DNA Complexes in Spheroids: Use and Limits

To elucidate the reasons underlying the poor penetration of non-viral vectors in tissues, relating transport properties to physico-chemical parameters of vectors may be crucial. These properties can be influenced by the presence of multiples labels that are used. Therefore utilizing a vector with minimum of labels preferably not more than one is important to studying penetration in tissues. The cell impermeant bisintercalating dye YOYO-1 was found suitable to both monitor the formation of complexes between DNA and an amphipathic peptide LK15 and, to track their penetration in HCT116 spheroids by confocal microscopy. The results revealed a limited decrease of fluorescence ascribed to the high affinity of YOYO-1 to bind DNA. The residual fluorescence of complexes can be exploited to monitor penetration into spheroids, after correction for YOYO-1 attenuation, and to revealing hyaluronidase-induced reduced binding. Hence high affinity dyes such as YOYO-1 with inefficiently quenched fluorescence may be important to establish a relation between novel medicines characteristics and penetration in tissues.     

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

Background  

Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.     

Gaining Insights on the Interactions of a Class of Decorated (2-([2,2′-Bipyridin]-6-yl)phenyl)platinum Compounds with c-Myc Oncogene Promoter G-Quadruplex and Other DNA Structures

Organometallic molecules offer some of the most promising scaffolds for interaction with G-quadruplex nucleic acids. We report the efficient synthesis of a family of organoplatinum(II) complexes, featuring a 2-([2,2′-bipyridin]-6-yl)phenyl tridentate (N^∧N^∧C) ligand, that incorporates peripheral side-chains aiming at enhancing and diversifying its interaction capabilities. These include a di-isopropyl carbamoyl amide, a morpholine ethylenamide, two enantiomeric proline imides and an oxazole. The binding affinities of the Pt-complexes were evaluated via UV-vis and fluorescence titrations, against 5 topologically-distinct DNA structures, including c-myc G-quadruplex, two telomeric (22AG) G-quadruplexes, a duplex (ds26) and a single-stranded (polyT) DNA. All compounds exhibited binding selectivity in favour of c-myc, with association constants (K_a) in the range of 2–5×10⁵ M⁻¹, lower affinity for both folds of 22AG and for ds26 and negligible affinity for polyT. Remarkable emission enhancements (up to 200-fold) upon addition of excess DNA were demonstrated by a subset of the compounds with c-myc, providing a basis for optical selectivity, since optical response to all other tested DNAs was low. A c-myc DNA-melting experiment showed significant stabilizing abilities for all compounds, with the most potent binder, the morpholine-Pt-complex, exhibiting a ΔT_m>30 °C, at 1 : 5 DNA-to-ligand molar ratio. The same study implied contributions of the diverse side-chains to helix stabilization. To gain direct evidence of the nature of the interactions, mixtures of c-myc with the four most promising compounds were studied via UV Resonance Raman (UVRR) spectroscopy, which revealed end-stacking binding mode, combined with interactions of side-chains with loop nucleobase residues. Docking simulations were conducted to provide insights into the binding modes for the same four Pt-compounds, suggesting that the binding preference for two alternative orientations of the c-myc G-quadruplex thymine ‘cap’ (‘open’ vs. ‘closed’), as well as the relative contributions to affinity from end-stacking and H-bonding, are highly dependent on the nature of the interacting Pt-complex side-chain.