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91.
A variety of human cancers become resistant or are intrinsically resistant to treatment with conventional chemotherapy, a phenomenon called multidrug resistance. This broad-based resistance results in large part, but not solely, from overexpression of members of the ATP-binding cassette (ABC) superfamily of membrane transporters, including P-glycoprotein, various members of the multidrug resistance associated proteins (MRPs), and ABCG2, also known as MXR1, BCRP, and ABCP. When overexpressed in cell lines, ABCG2 has the ability to confer high levels of resistance to anthracyclines, mitoxantrone, bisantrene, and the camptothecins topotecan and SN-38. This review focuses on the discovery, the biochemistry and the normal physiology of human ABCG2, a novel ABC half transporter expressed abundantly in placenta, as well as in liver, intestine and stem cells. ABCG2 may serve a protective function by preventing toxins from entering cells as well as potentially playing a role in regulating stem cell differentiation. We also discuss the involvement of ABCG2 in multidrug resistance in cancer, especially with regard to acute myeloid leukemia. The mechanism by which substrates are recognized by ABCG2 and how the energy of ATP hydrolysis is transduced into transport remain elusive. A complete understanding of the mechanism and biological function of ABCG2 will be important for understanding its normal physiology as well as potentially for the development of novel chemotherapeutic treatment strategies. 相似文献
92.
Sophie Griveau Dimitri Mercier Christine Vautrin-Ul Annie Chauss 《Electrochemistry communications》2007,9(12):2768-2773
We propose in this study a simple and rapid way to produce stable amino-derivatized conductive surfaces for the subsequent immobilization of (bio)molecules. This was achieved through the use of (4-aminoethyl)benzenediazonium salt (AEBD), which was immobilized on glassy carbon and gold electrodes by its electrochemical reduction. The presence of terminal grafted amino functions was evidenced with XPS by analyzing N1s core level. Besides this conventional surface characterisation, an electrochemical strategy is proposed here to evidence the presence of immobilized amines, in which the chemical reactivity of amines towards 2,4,6-trinitrobenzenesulfonic acid (TNBS) is used. Surface-bound TNBS served as an electrochemical marker and was detected by cyclic voltammetry. Additionally, pre-modified gold electrodes with amino functions can be derivatized with biomolecules such as glutathione (GSH). Glutathione attachment was evidenced by studying the electrochemical behaviour of ferri/ferrocyanide redox before and after its immobilization. The functionalized electrodes were then used for the detection of copper ions in neutral aqueous solutions. 相似文献
93.
The new tetra-aryl trans-A2B2-porphyrin with two fluoren-2-yl and two phenyl groups at the meso-positions has been synthesized and characterized, together with the analogous bi-aryl trans-A2-porphyrin incorporating only the fluorenyl groups. The photophysical properties of these new compounds in solution are reported. The two additional phenyl groups in the A2B2 porphyrin stabilize the first excited singlet state by approximately 500 cm−1 compared to the A2 system, as revealed by the red-shift of the absorption Q bands and of the fluorescence emission bands. Both compounds display enhanced emission quantum yields compared to tetraphenylporphyrin: the augmentation is higher for the tetra-aryl than for the bi-aryl system, although not as high as for tetrafluorenylporphyrin. Fluorescence lifetime measurements of the series of four compounds suggest that the trends can be interpreted in terms of the larger influence of fluorenyl over phenyl groups in increasing the fluorescence radiative rate constant of the porphyrin, kf. 相似文献
94.
Petre BA Youhnovski N Lukkari J Weber R Przybylski M 《European journal of mass spectrometry (Chichester, England)》2005,11(5):513-518
Nitration of tyrosine residues in proteins may occur in cells upon oxidative stress and inflammation processes mediated through generation of reactive nitroxyl from peroxynitrite. Tyrosine nitration from oxidative pathways may generate cytotoxic species that cause protein dysfunction and pathogenesis. A number of protein nitrations in vivo have been reported and some specific Tyrosine nitration sites have been recently identified using mass spectrometric methods. High-resolution Fourier transform ion cyclotron resonance mass spectrometry (MALDI) FT-ICR-MS) is shown here to be a highly efficient method in the determination of protein nitrations. Following the identification of nitration of the catalytic site Tyr-430 residue of bovine prostacyclin synthase, we synthesised several model peptides containing both unmodified tyrosine and 3-nitro-tyrosine residues, using solid-phase peptide synthesis (SPPS). The structures of the nitrotyrosine peptides were characterised both by ESI- and by matrix-assisted laser desorption/ionisation (MALDI)-FT-ICR-MS, using a standard ultraviolet (UV) nitrogen nitrogen laser and a 2.97 microm Nd-YAG infrared laser. Using UV-MALDI-MS, 3-nitrotyrosyl-peptides were found to undergo extensive photochemical fragmentation at the nitrophenyl group, which may hamper or prevent the unequivocal identification of Tyr-nitrations in cellular proteins. In contrast, infrared-MALDI-FT-ICR-MS did not produce fragmentation of molecular ions of Tyr-nitrated peptides. 相似文献
95.
Starting from aspartic acid, we synthesized lactam-bridged beta- and gamma-amino acid equivalents. Using the 1,4-bis-electrophile 1b as a central intermediate, the 4- and 5-aminopiperidin-2-ones 4 and 8, respectively, were approached by regioselective functionalization and subsequent lactamization. Diastereoselective C-alkylation was performed after N-protection of the lactam functionality when exclusive trans configuration resulting in the formation of 5a-f was observed in the 4-amino series. On the other hand, cis selectivity was typical for the alkylations of the 5-amino lactams 5a,b. To investigate the ability of the lactam building blocks to induce reverse-turn structures by intramolecular hydrogen bonding, the model peptidomimetics 12 and 14 representing Homo-Freidinger lactams of type II and III were prepared from 4a and 8a, respectively. Conformational analyses in dilute solution (1 mM) by IR and NMR spectroscopy at room temperature clearly indicated that the 4-aminopiperidin-2-one derivative 12 predominantly adopts a reverse-turn structure stabilized by a CO-HN hydrogen bond in an 11-membered ring. VT NMR experiments showed a substantial temperature dependency of the terminal NH when Deltadelta(NH)/DeltaT = -6.5 indicated that the amount of intramolecular hydrogen bonding is higher at low temperature. An application in the field of medicinal chemistry was demonstrated. Thus, starting from the Homo-Freidinger lactam 11c and the enantiomer ent-11c, we synthesized the peptidomimetics 15c and 16c and investigated them as lactam-bridged analogues of the dopamine receptor modulating peptide Pro-Leu-Gly-NH(2) (PLG). Both test compounds turned out to enhance significantly the agonist binding of dopamine D2 receptors, when the isomer 15c revealed a potency comparable to the genuine ligand PLG. 相似文献
96.
Heavy Metal Chelates of α-Cyano-β-amino-dithioacrylates The inner metal chelates of PdII, NiII, CoIII, and AgI with α-cyano-β-amino-dithioacrylates have been prepared. The coordination of the dithioester group and the amine nitrogen (S/N-coordination) has been proved by the chemical shift of the S2p and N1s electron binding energies in the ESCA spectra. 相似文献
97.
Retsek JL Drain CM Kirmaier C Nurco DJ Medforth CJ Smith KM Sazanovich IV Chirvony VS Fajer J Holten D 《Journal of the American Chemical Society》2003,125(32):9787-9800
The ground- and excited-state metal-ligand dynamics of nonplanar nickel(II) 2,3,5,7,8,10,12,13,15,17,18,20-dodecaphenylporphyrin (NiDPP) and two fluorinated analogues (NiF(20)DPP and NiF(28)DPP) have been investigated using static and time-resolved absorption spectroscopy in toluene and in ligating media that differ in basicity, aromaticity, and steric encumbrance. Because of the electronic and steric consequences of nonplanarity, NiDPP does not bind axial ligands in the ground state, but metal coordination does occur after photoexcitation with multistep dynamics that depend on the properties of the ligand. Following the structural relaxations that occur in all nickel porphyrins within approximately 10 ps, ligand binding to photoexcited NiDPP is progressively longer in pyridine, piperidine, and 3,5-lutidine (25-100 ps) but does not occur at all in 2,6-lutidine in which the ligating nitrogen is sterically encumbered. The transient intermediate that is formed, which nominally could be either a five- or six-coordinate species, also has a ligand-dependent lifetime (200-550 ps). Decay of this intermediate occurs partially via ligand release to re-form the uncoordinated species, in competition with binding of the second axial ligand and/or conformational/electronic relaxations (of a six-coordinate intermediate) to give the ground state of the bis-ligated photoproduct. The finding that the photoproduct channel principally depends on ligand characteristics along with the time-evolving spectra suggests that the transient intermediate may involve a five-coordinate species. In contrast to NiDPP, the fluorinated analogues NiF(20)DPP and NiF(28)DPP do coordinate axial ligands in the ground state but eject them after photoexcitation. Collectively, these results demonstrate the sensitivity with which the electronic and structural characteristics of the macrocycle, substituents, and solvent (ligands) can govern the photophysical and photochemical properties of nonplanar porphyrins and open new avenues for exploring photoinduced ligand association and dissociation behavior. 相似文献
98.
Separation of the enzymes formate dehydrogenase, formaldehyde dehydrogenase and methanol oxidase from Candida boidinii crude extract has been explored using continuous flow zone electrophoresis in the VaP-22 and the scaled-up VaP-220 electrophoresis apparatus. Yields up to 95% and purification factors between 3 and 7 were obtained, together with separation of cell debris from the enzymes. Multiple injections of sample were used to obtain a protein throughput of 46.2 mg/h in the VaP-22. A tenfold higher throughput was achieved using the VaP-220. Correlation of the electrophoretic mobility in continuous flow zone electrophoresis with the elution behavior in ion-exchange chromatography confirmed the primary role of net surface charge in the separation of biological molecules. Proteins and enzymes with differences greater than 0.05 M elution molarities in ion-exchange chromatography can be separated. This corresponds to a preparative scale (mg/h or g/h) separation of proteins and enzymes whose difference in apparent electrophoretic mobility is greater than 0.70 x 10(-5) cm2/(V.s). 相似文献
99.
A solution-phase synthesis of bicyclic prolines containing four points of diversity has been developed by a two-step synthesis involving 1,3-dipolar cycloaddition of perfluoroalkylsulfonyl-protected hydroxybenzaldehydes followed by Pd-catalyzed Suzuki coupling reaction of fluorous sulfonates with boronic acids. Both reactions are conducted under microwave irradiation and reaction mixtures are purified by solid-phase extractions without performing chromatography. 相似文献
100.
W. Grüner R. Giegerich D. Strothmann C. Reidys J. Weber I. L. Hofacker P. F. Stadler P. Schuster 《Monatshefte für Chemie / Chemical Monthly》1996,127(4):355-374
Summary Global relations between RNA sequences and secondary structures are understood as mappings from sequence space into shape space. These mappings are investigated by exhaustive folding of allGC andAU sequences with chain lengths up to 30. The computed structural data are evaluated through exhaustive enumeration and used as an exact reference for testing analytical results derived from mathematical models and sampling based on statistical methods. Several new concepts of RNA sequence to secondary structure mappings are investigated, among them that ofneutral networks (being sets of sequences folding into the same structure). Exhaustive enumeration allows to test several previously suggested relations: the number of (minimum free energy) secondary structures as a function of the chain length as well as the frequency distribution of structures at constant chain length (commonly resulting in generalized forms ofZipf's law).
Analyse der Beziehungen zwischen RNA-Sequenzen und Sekundärstrukturen durch vollständige Faltung, 1. Mitt. Faltung, Neutrale Netzwerke
Zusammenfassung Die globalen Benziehungen zwischen RNA-Sequenzen und Sekundärstrukturen werden als Abbildungen aus einem Raum aller Sequenzen in einen Raum aller Strukturen aufgefaßt. Diese Abbildungen werden durch Falten aller binären Sequenzen desGC-undAU-Alphabets mit Kettenlängen bis zun=30 untersucht. Die berechneten Strukturdaten werden durch vollständiges Abzählen ausgewertet und als eine exakte Referenz zum Überprüfen analytischer Resultate aus mathematischen Modellen sowie zum Testen statistisch erhobener Proben verwendet. Einige neuartige Konzepte zur Beschreibung der Beziehungen zwischen Sequenzen und Strukturen werden eingehend untersucht, unter ihnen der Begriff derneutralen Netzwerke. Ein neutrales Netzwerk besteht aus allen Sequenzen, die eine bestimmte Struktur ausbilden. Vollständiges Abzählen ermöglicht beispielsweise die Bestimmung aller Strukturen minimaler freier Energie in Abhängigkeit von der Kettenlänge ebenso wie die Bestimmung der Häufigkeitsverteilungen der Strukturen bei konstanten Kettenlängen. Die letzteren folgen einer verallgemeinerten FormZipfschen Gesetzes.相似文献