The Experts below are selected from a list of 9591 Experts worldwide ranked by ideXlab platform
Jens Ulstrup - One of the best experts on this subject based on the ideXlab platform.
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ordered assembly and controlled electron transfer of the blue copper protein azurin at gold 111 single crystal substrates
Journal of Physical Chemistry B, 2001Co-Authors: Qijin Chi, Jingdong Zhang, Jens Enevold Thaulov Andersen, Jens UlstrupAbstract:We have shown that Pseudomonas aeruginosa azurin can be immobilized on alkanethiol monolayers self-assembled on Au(111). Immobilization is achieved through hydrophobic interactions between the hydrophobic area around the copper atom in azurin and methyl heads of alkanethiol to form submonolayers or monolayers. In this orientation mode azurin molecules on Au(111) are oriented with the redox center (copper atom) facing the electrode surface. This is opposite to the orientation of azurin on bare gold which is via a surface Disulfide Group such as recently reported. Scanning tunneling microscopy (STM) with molecular resolution reveals that both well-ordered alkanethiol and protein adlayers are present. Adsorbed azurin molecules exhibit high stability and retain electron transfer (ET) function. Long-range interfacial ET between azurin and Au(111) across variable-length alkanethiol bridges was systematically investigated by different electrochemical techniques. Distance-dependent ET can be controlled by adjusti...
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molecular monolayers and interfacial electron transfer of pseudomonas aeruginosa azurin on au 111
Journal of the American Chemical Society, 2000Co-Authors: Qijin Chi, Jingdong Zhang, Jens Enevold Thaulov Andersen, Esben Peter Friis, Gerard W Canters, Jens Ulrik Nielsen, Ib Chorkendorff, Jens UlstrupAbstract:We provide a comprehensive approach to the formation and characterization of molecular monolayers of the blue copper protein Pseudomonas aeruginosa azurin on Au(111) in aqueous ammonium acetate solution. Main issues are adsorption patterns, reductive desorption, properties of the double layer, and long-range electrochemical electron transfer between the electrode and the copper center. Voltammetry, electrochemical impedance spectroscopy (EIS), in situ scanning tunneling microscopy (STM), and X-ray photoelectron spectroscopy (XPS) have been employed to disclose features of these issues. Zn-substituted azurin, cystine, and 1-butanethiol are investigated for comparison. Cyclic voltammetric and capacitance measurements show qualitatively that azurin is adsorbed at submicromolar concentrations over a broad potential range. The characteristics of reductive desorption suggest that azurin is adsorbed via its Disulfide Group to form a monolayer. The adsorption of this protein on Au(111) via a gold−sulfur binding m...
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an approach to long range electron transfer mechanisms in metalloproteins in situ scanning tunneling microscopy with submolecular resolution
Proceedings of the National Academy of Sciences of the United States of America, 1999Co-Authors: Esben Peter Friis, Jingdong Zhang, Jens Enevold Thaulov Andersen, Yu I Kharkats, A M Kuznetsov, Richard J Nichols, Jens UlstrupAbstract:Abstract In situ scanning tunneling microscopy (STM) of redox molecules, in aqueous solution, shows interesting analogies and differences compared with interfacial electrochemical electron transfer (ET) and ET in homogeneous solution. This is because the redox level represents a deep indentation in the tunnel barrier, with possible temporary electronic population. Particular perspectives are that both the bias voltage and the overvoltage relative to a reference electrode can be controlled, reflected in spectroscopic features when the potential variation brings the redox level to cross the Fermi levels of the substrate and tip. The blue copper protein azurin adsorbs on gold(111) via a surface Disulfide Group. Well resolved in situ STM images show arrays of molecules on the triangular gold(111) terraces. This points to the feasibility of in situ STM of redox metalloproteins directly in their natural aqueous medium. Each structure also shows a central brighter contrast in the constant current mode, indicative of 2- to 4-fold current enhancement compared with the peripheral parts. This supports the notion of tunneling via the redox level of the copper atom and of in situ STM as a new approach to long-range electron tunneling in metalloproteins.
Mingzu Zhang - One of the best experts on this subject based on the ideXlab platform.
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efficient click synthesis of a protonized and reduction sensitive amphiphilic small molecule prodrug containing camptothecin and gemcitabine for a drug self delivery system
Molecular Pharmaceutics, 2019Co-Authors: Shuxiang Dong, Yue Sun, Mingzu ZhangAbstract:Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin-ss-1,2,3-triazole-gemcitabine conjugate (abbreviated as CPT-ss-triazole-GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. To obtain this drug-triazole-drug conjugate, we first prepared a CPT derivate containing a propargyl Group linked with a Disulfide Group and a GEM derivate attached to an azide Group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide Groups to yield the CPT-ss-triazole-GEM prodrug. The characterizations of chemical structures of these intermediates and the final product were performed by 1H NMR, Fourier transform infrared, and liquid chromatography/mass spectrometry measurements. This amphiphilic small-molecule drug-triazole-drug conjugate displayed a high drug loading content, that is, 36.0% of CPT and 27.2% of GEM. This kind of amphiphilic small-molecule prodrugs could form spherical nanoparticles in an aqueous solution in the absence of any other polymeric carriers, in which the hydrophobic CPT formed the core of the nanoparticles, whereas the hydrophilic GEM and protonated 1,2,3-triazole Group yielded the shell. In the tumor microenvironment, the prodrug nanoparticles could release both pristine drugs simultaneously. Under the conditions of pH 7.4, and pH 7.4 and 2 μM glutathione (GSH), the prodrug nanoparticles could maintain stability and only 7% of CPT was leaked. However, in a high-GSH environment (pH 7.4 and 10 mM GSH) with the same incubation time, the Disulfide linkage would be dissociated and lead to about 34% of CPT release. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test demonstrated that these prodrug nanoparticles showed a higher cytotoxicity toward HepG2 cells than free CPT and free GEM on both 48 and 72 h of incubation. Both in vitro cellular uptake and flow cytometry results implied that these prodrug nanoparticles could be internalized by HepG2 cells with efficient drug release inside cells. The pharmacokinetics and tissue distribution of the prodrug showed a moderate half-life in vivo, and the prodrug peak concentration in most of the collected tissues appeared at 0.25 h after administration. In addition, the CPT-ss-triazole-GEM prodrug could not cross the blood-brain barrier. Even more important is the fact that there is no accumulation in tissues and a rapid elimination of this small-molecule prodrug could be achieved. In brief, this protonized and reduction-sensitive prodrug simultaneously binds both antitumor drugs and has good self-delivery behavior through the donor-acceptor interaction of the H-bonding ligand, that is, the 1,2,3-triazole Group. It provides a new method for combined drug therapy.
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efficient click synthesis of a protonized and reduction sensitive amphiphilic small molecule prodrug containing camptothecin and gemcitabine for a drug self delivery system
Molecular Pharmaceutics, 2019Co-Authors: Shuxiang Dong, Yue Sun, Mingzu ZhangAbstract:Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin–ss-1,2,3-triazole–gemcitabine conjugate (abbreviated as CPT–ss-triazole–GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction. To obtain this drug–triazole–drug conjugate, we first prepared a CPT derivate containing a propargyl Group linked with a Disulfide Group and a GEM derivate attached to an azide Group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide Groups to yield the CPT–ss-triazole–GEM prodrug. The characterizations of chemical structures of these intermediates a...
Bouchra Gharib - One of the best experts on this subject based on the ideXlab platform.
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protection against cerebral malaria by the low molecular weight thiol pantethine
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Marie-france Penet, Emilie Cornille, Max De Reggi, Mhamad Abouhamdan, Nicolas Coltel, Georges E Grau, Bouchra GharibAbstract:We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The Disulfide Group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.
Shuxiang Dong - One of the best experts on this subject based on the ideXlab platform.
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efficient click synthesis of a protonized and reduction sensitive amphiphilic small molecule prodrug containing camptothecin and gemcitabine for a drug self delivery system
Molecular Pharmaceutics, 2019Co-Authors: Shuxiang Dong, Yue Sun, Mingzu ZhangAbstract:Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin-ss-1,2,3-triazole-gemcitabine conjugate (abbreviated as CPT-ss-triazole-GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. To obtain this drug-triazole-drug conjugate, we first prepared a CPT derivate containing a propargyl Group linked with a Disulfide Group and a GEM derivate attached to an azide Group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide Groups to yield the CPT-ss-triazole-GEM prodrug. The characterizations of chemical structures of these intermediates and the final product were performed by 1H NMR, Fourier transform infrared, and liquid chromatography/mass spectrometry measurements. This amphiphilic small-molecule drug-triazole-drug conjugate displayed a high drug loading content, that is, 36.0% of CPT and 27.2% of GEM. This kind of amphiphilic small-molecule prodrugs could form spherical nanoparticles in an aqueous solution in the absence of any other polymeric carriers, in which the hydrophobic CPT formed the core of the nanoparticles, whereas the hydrophilic GEM and protonated 1,2,3-triazole Group yielded the shell. In the tumor microenvironment, the prodrug nanoparticles could release both pristine drugs simultaneously. Under the conditions of pH 7.4, and pH 7.4 and 2 μM glutathione (GSH), the prodrug nanoparticles could maintain stability and only 7% of CPT was leaked. However, in a high-GSH environment (pH 7.4 and 10 mM GSH) with the same incubation time, the Disulfide linkage would be dissociated and lead to about 34% of CPT release. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test demonstrated that these prodrug nanoparticles showed a higher cytotoxicity toward HepG2 cells than free CPT and free GEM on both 48 and 72 h of incubation. Both in vitro cellular uptake and flow cytometry results implied that these prodrug nanoparticles could be internalized by HepG2 cells with efficient drug release inside cells. The pharmacokinetics and tissue distribution of the prodrug showed a moderate half-life in vivo, and the prodrug peak concentration in most of the collected tissues appeared at 0.25 h after administration. In addition, the CPT-ss-triazole-GEM prodrug could not cross the blood-brain barrier. Even more important is the fact that there is no accumulation in tissues and a rapid elimination of this small-molecule prodrug could be achieved. In brief, this protonized and reduction-sensitive prodrug simultaneously binds both antitumor drugs and has good self-delivery behavior through the donor-acceptor interaction of the H-bonding ligand, that is, the 1,2,3-triazole Group. It provides a new method for combined drug therapy.
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efficient click synthesis of a protonized and reduction sensitive amphiphilic small molecule prodrug containing camptothecin and gemcitabine for a drug self delivery system
Molecular Pharmaceutics, 2019Co-Authors: Shuxiang Dong, Yue Sun, Mingzu ZhangAbstract:Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin–ss-1,2,3-triazole–gemcitabine conjugate (abbreviated as CPT–ss-triazole–GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reaction. To obtain this drug–triazole–drug conjugate, we first prepared a CPT derivate containing a propargyl Group linked with a Disulfide Group and a GEM derivate attached to an azide Group. Subsequently, the two kinds of modified drugs were connected together through a CuAAC reaction between the alkynyl and azide Groups to yield the CPT–ss-triazole–GEM prodrug. The characterizations of chemical structures of these intermediates a...
Marie-france Penet - One of the best experts on this subject based on the ideXlab platform.
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protection against cerebral malaria by the low molecular weight thiol pantethine
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Marie-france Penet, Emilie Cornille, Max De Reggi, Mhamad Abouhamdan, Nicolas Coltel, Georges E Grau, Bouchra GharibAbstract:We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The Disulfide Group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.