0000000000067469
AUTHOR
Antonio Garcia-españa
Modulation of DNA binding by reversible metal-controlled molecular reorganizations of scorpiand-like ligands.
DNA interaction with scorpiand azamacrocycles has been achieved through modulation of their binding affinities. Studies performed with different experimental techniques provided evidence that pH or metal-driven molecular reorganizations of these ligands regulate their ability to interact with calf thymus DNA (ctDNA) through an intercalative mode. Interestingly enough, metal-driven molecular reorganizations serve to increase or decrease the biological activities of these compounds significantly.
Significant in vivo anti-inflammatory activity of Pytren4Q-Mn a superoxide dismutase 2 (SOD2) mimetic scorpiand-like Mn (II) complex.
Background The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight. Background/Methodology We have recently reported that two SOD mimetic compounds, the MnII complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q MnII complexes, in cultured macrophages …
Ditopic Aza-Scorpiand Ligands Interact Selectively with ds-RNA and Modulate the Interaction upon Formation of Zn2+ Complexes
Nucleic acids are essential biomolecules in living systems and represent one of the main targets of chemists, biophysics, biologists, and nanotechnologists. New small molecules are continuously developed to target the duplex (ds) structure of DNA and, most recently, RNA to be used as therapeutics and/or biological tools. Stimuli-triggered systems can promote and hamper the interaction to biomolecules through external stimuli such as light and metal coordination. In this work, we report on the interaction with ds-DNA and ds-RNA of two aza-macrocycles able to coordinate Zn2+ metal ions and form binuclear complexes. The interaction of the aza-macrocycles and the Zn2+ metal complexes with duple…
Nanog Regulates Proliferation During Early Fish Development
Abstract Nanog is involved in controlling pluripotency and differentiation of stem cells in vitro. However, its function in vivo has been studied only in mouse embryos and various reports suggest that Nanog may not be required for the regulation of differentiation. To better understand endogenous Nanog function, more animal models should be introduced to complement the murine model. Here, we have identified the homolog of the mammalian Nanog gene in teleost fish and describe the endogenous expression of Ol-Nanog mRNA and protein during medaka (Oryzias latipes) embryonic development and in the adult gonads. Using medaka fish as a vertebrate model to study Nanog function, we demonstrate that …
Analysis of the Ush2a Gene in Medaka Fish (Oryzias latipes)
Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for ge…
Mn(II) complexes of scorpiand-like ligands. A model for the MnSOD active centre with high in vitro and in vivo activity
Manganese complexes of polyamines consisting of an aza-pyridinophane macrocyclic core functionalised with side chains containing quinoline or pyridine units have been characterised by a variety of solution techniques and single crystal x-ray diffraction. Some of these compounds have proved to display interesting antioxidant capabilities in vitro and in vivo in prokaryotic (bacteria) and eukaryotic (yeast and fish embryo) organisms. In particular, the Mn complex of the ligand containing a 4-quinoline group in its side arm which, as it happens in the MnSOD enzymes, has a water molecule coordinated to the metal ion that shows the lowest toxicity and highest functional efficiency both in vitro …
Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands.
The Mn2+ coordination chemistry of double scorpiand ligands in which two polyazacyclophane macrocycles have been connected by pyridine, phenanthroline and bipyridine spacers has been studied by potentiometry, paramagnetic NMR and electrochemistry. All ligands show high stability with Mn2+ and the complexes were formed in a wide pH range. DFT calculations support the structures and coordination geometries derived from the study. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three systems were tested as anti-inflammatory drugs in human macrophages measuring the accumulation of cyto…
Homo- and Heterobinuclear Cu2+ and Zn2+ Complexes of Ditopic Aza Scorpiand Ligands as Superoxide Dismutase Mimics
Two polytopic aza-scorpiand-like ligands, 6-[7-(diaminoethyl)-3,7-diazaheptyl]-3,6,9-triaza-1-(2,6-pyridina)cyclodecaphane (L1) and 6-[6′-[3,6,9-triaza-1-(2,6-pyridina)cyclodecaphan-6-yl]-3-azahexyl]-3,6,9-triaza-1-(2,6-pyridina)cyclodecaphane (L2), have been synthesized. The acid–base behavior and Cu2+, Zn2+, and Cu2+/Zn2+ mixed coordination have been analyzed by potentiometry, cyclic voltammetry, and UV–vis spectroscopy. The resolution of the crystal structures of [Cu2L2Cl2](ClO4)2·1.67H2O (1), [Cu2HL2Br2](ClO4)3·1.5H2O (2), and [CuZnL2Cl2](ClO4)2·1.64H2O (3) shows, in agreement with the solution data, the formation of homobinuclear Cu2+/Cu2+ and heterobinuclear Cu2+/Zn2+ complexes. The m…