Apoptotic and anti-tumor activities of metallo-salens

The present invention describes the synthesis and biochemical activities of metallo-salen compounds and their derivatives. The Mn(III)-salen and Fe(III)-salen derivatives of the present invention are potential anti-tumor agents, that affect cell viability, induce strong apoptotic activity, cause nuclear condensation, fragmentation, and ultimately death in breast cancer cells MCF-7.Board of Regents, University of Texas Syste

Metal-ion-dependent oxidative DNA cleavage by transition metal complexes of a new water-soluble salen derivative

A new water-soluble, salen [salen = bis(salicylidene) ethylenediamine]-based ligand, 3 was developed. Two of the metal complexes of this ligand, i.e., 3a, [Mn(III)] and 3b, [Ni(II)], in the presence of cooxidant magnesium monoperoxyphthalate (MMPP) cleaved plasmid DNA pTZ19R efficiently and rapidly at a concentration ≈ 1 μM. In contrast, under comparable conditions, other metal complexes 3c, [Cu(II)] or 3d, [Cr(III)] could not induce any significant DNA nicking. The findings with Ni(II) complexes suggest that the DNA cleavage processes can be modulated by the disposition of charges around the ligand

The human PAF complex coordinates transcription with events downstream of RNA synthesis.

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates 3\u27-5\u27 mRNA degradation. However, hSKI complex localizes to both nucleus and cytoplasm. Immunoprecipitation experiments revealed that hPAF and hSKI complexes interact, and ChIP experiments demonstrated that hSKI associates with transcriptionally active genes dependent on the presence of hPAF. Thus, in addition to coordinating events during transcription (initiation, promoter clearance, and elongation), hPAF also coordinates events in RNA quality control

Evidence of interlipidic ion-pairing in anion-induced DNA release from cationic amphiphile-DNA complexes. Mechanistic implications in transfection

Complex formation of DNA with a number of cationic amphiphiles has been examined using fluorescence, gel electrophoresis, and chemical nuclease digestion. Here we have addressed the status of both DNA and lipid upon complexation with each other. DNA upon binding with cationic amphiphiles changes its structure in such a way that it loses the ability to intercalate and becomes resistant to nuclease digestion. Fluorescence anisotropy measurements due to 1,6-diphenylhexatriene (DPH) doped in cationic liposomes demonstrated that upon complexation with DNA, the resulting complexes still retain lamellar organizations with modest enhancement in thermal stabilities. The lipid-DNA complexation is most effective only when the complexation was carried out at or around the phase transition temperatures of the cationic lipid employed in the complexation with DNA. The release of DNA from cationic lipid-DNA complexes could be induced by several anionic additives. Determination of fluorescence anisotropies (due to DPH) as a function of temperature clearly demonstrates that the addition of equivalent amounts of anionic amphiphile into cationic lipid-DNA complexes leads to the ion-pairing of the amphiphiles, the melting profiles of which are virtually the same as those obtained in the absence of DNA. In this process DNA gets released from its complexes with cationic lipids and regains its natural intercalation ability, movement, and staining ability on agarose gel and also the sensitivities toward nuclease digestion. This clearly suggests that combination of ion-pairing and hydrophobic interactions between cationic and anionic amphiphiles is stronger than the electrostatic forces involved in the cationic lipid-DNA complexation. It is further revealed that the DNA release by anions is most efficient from the cationic lipid-DNA complexes at or around the T-m of the cationic lipid used in DNA complexation. This explains why more effective DNA delivery is achieved with cationic lipids that bear unsaturated hydrocarbon chains than with their saturated hydrocarbon counterparts

Ambient Oxygen Activating Water Soluble Cobalt-Salen Complex for DNA Cleavage

A new water-soluble Co-II-salen complex cleaves DNA spontaneously under ambient aerobic conditions; the cleavage is further enhanced by inclusion of 2 mmol dm(-3) dithiothreitol in the reaction buffer

DNA cleavage by intercalatable cobalt-bispicolylamine complexes activated by visible light

Two intercalatable Co-II-complexes of anthryl or anthraquinone attached bispicolylamine derivatives cleave plasmid pTZ19R DNA spontaneously upon exposure to visible light under ambient conditions