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Target Complex (target + complex)

Distribution by Scientific Domains

Life Sciences	50%
Chemistry	50%

Selected Abstracts

CE-ESI-MS/MS as a rapid screening tool for the comparison of protein,ligand interactions

ELECTROPHORESIS, Issue 7 2010
Thomas Hoffmann
Abstract In drug development, the combinatorial synthesis of drug libraries is common use, therefore efficient tools for the characterization of drug candidates and the extent of interaction between a drug and its target protein is a central question of analytical interest. While biological activity is tested today by enzyme assays, MS techniques attract more and more attention as an alternative for a rapid comparison of drug,target interactions. CE enables the separation of proteins and drug,enzyme complexes preserving their physiological activity in aqueous media. By hyphenating CE with ESI-MS/MS, the binding strength of enzyme inhibitors can be deduced from MS/MS experiments, which selectively release the inhibitor from the drug,target complex after CID. In this study, ,-chymotrypsin (CT), a serine protease, was chosen as a model compound. Chymostatin is a naturally occurring peptide aldehyde binding to CT through a hemiacetal bond and electrostatic interaction. First, a CE separation was developed, which allows the analysis of ,-CT and a chymotrypsin,chymostatin complex under MS-compatible conditions. The use of neutral-coated CE capillaries was mandatory to reduce analyte,wall interactions. ESI-quadrupole ion trap-MS was worked out to demonstrate the selective drug release after CID. Fragmentation of the drug,enzyme complex was monitored in dependence from the excitation energy in the ion trap, leading to the V50 voltage that enables 50% complex fragmentation as a reference value for chymotrypsin,chymostatin complex. A stable CE-ESI-MS/MS setup was established, which preserves the drug,enzyme complexes during ionization,desolvation processes. With this optimized setup, different CT inhibitors could be investigated and compared. [source]

Highly Efficient Visible-Light-Induced Photocleavage of DNA by a Ruthenium-Substituted Fluorinated Porphyrin

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 11 2009
Michelle Cunningham
Abstract A new porphyrin, meso -5-(pentafluorophenyl)-10,15,20-tris(4-pyridyl)porphyrin, has been synthesized. Coordination of two [Ru(bipy)2Cl]+ moieties (where bipy = 2,2,-bipyridine) to the pyridyl nitrogen atoms in the 10,15-positions gives the target complex. Electronic transitions associated with the ruthenium,porphyrin include an intense Soret band and four less intense Q-bands in the visible region of the spectrum. An intense ,,,* transition in the UV region associated with the bipyridyl groups and a metal-to-ligand charge-transfer (MLCT) band appearing as a shoulder to the Soret band are also observed. Electrochemical properties associated with the complex include a redox couple in the cathodic region with E1/2 = ,0.84 V vs. Ag/AgCl attributed to the porphyrin and a redox couple in the anodic region at E1/2 = 0.79 V vs. Ag/AgCl due to the RuIII/II couple. DNA titrations and ethidium bromide displacement experiments indicate the ruthenium porphyrin interacts with DNA potentially through a partial intercalation mechanism. Irradiation of aqueous solutions of the ruthenated complex and supercoiled DNA at a 100:1 base pair/complex ratio with visible light above 400 nm indicates that the complex causes double-strand breaks of the DNA.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Enhancement and rescue of target capture in Tn10 transposition by site-specific modifications in target DNA

MOLECULAR MICROBIOLOGY, Issue 4 2004
Patrick A. Pribil
Summary The bacterial transposon Tn10 inserts preferentially into specific target sequences. This insertion specificity appears to be linked to the ability of target sites to adopt symmetrically positioned DNA bends after binding the transposition machinery. Target DNA bending is thought to permit the transposase protein to make additional contacts with the target DNA, thereby stabilizing the target complex so that the joining of transposon and target DNA sequences can occur efficiently. In the current work, we have asked whether the introduction of a discontinuity in a target DNA strand, a modification that is expected to make it easier for a DNA molecule to bend, can enhance or rescue target capture under otherwise suboptimal reaction conditions. We show that either a nick or a missing phosphate specifically at the site of reaction chemistry increases the ability of various target DNAs to form the target capture complex. The result suggests that the bends in the target DNA are highly localized and include the scissile phosphates. This raises the possibility that strand transfer is mechanistically linked to target capture. We have also identified specific residues in the target DNA and in transposase that appear to play an important role in target DNA bending. [source]

Can Weakly Coordinating Anions Stabilize Mercury in Its Oxidation State +IV?

CHEMISTRY - A EUROPEAN JOURNAL, Issue 9 2005
Sebastian Riedel Dipl.-Chem.
Abstract While the thermochemical stability of gas-phase HgF4 against F2 elimination was predicted by accurate quantum chemical calculations more than a decade ago, experimental verification of "truly transition-metal" mercury(IV) chemistry is still lacking. This work uses detailed density functional calculations to explore alternative species that might provide access to condensed-phase HgIV chemistry. The structures and thermochemical stabilities of complexes HgIVX4 and HgIVF2X2 (X,=AlF4,, Al2F7,, AsF6,, SbF6,, As2F11,, Sb2F11,, OSeF5,, OTeF5,) have been assessed and are compared with each other, with smaller gas-phase HgX4 complexes, and with known related noble gas compounds. Most species eliminate F2 exothermically, with energies ranging from only about ,60 kJ,mol,1 to appreciable ,180 kJ,mol,1. The lower stability of these species compared to gas-phase HgF4 is due to relatively high coordination numbers of six in the resulting HgII complexes that stabilize the elimination products. Complexes with AsF6 ligands appear more promising than their SbF6 analogues, due to differential aggregation effects in the HgII and HgIV states. HgF2X2 complexes with X,=OSeF5, or OTeF5, exhibit endothermic fluorine elimination and relatively weak interactions in the HgII products. However, elimination of the peroxidic (OEF5)2 coupling products of these ligands provides an alternative exothermic elimination pathway with energies between ,120 and ,130 kJ,mol,1. While all of the complexes investigated here thus have one exothermic decomposition channel, there is indirect evidence that the reactions should exhibit nonnegligible activation barriers. A number of possible synthetic pathways towards the most interesting condensed-phase HgIV target complexes are proposed. [source]