排序方式: 共有37条查询结果,搜索用时 109 毫秒
1.
Yulin Ren Sijin Wu Joanna E. Burdette Xiaolin Cheng A. Douglas Kinghorn 《Molecules (Basel, Switzerland)》2021,26(12)
Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na+/K+-ATPase. The docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na+/K+-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na+/K+-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity. 相似文献
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Self-injection length in La0.7Ca0.3MnO3-YBa2Cu3O7-δ ferromagnet-superconductor multilayer thin films
We have carried out extensive studies on the self-injection problem in barrierless heterojunctions between La0.7Ca0.3MnO3 (LCMO) and YBa2Cu3O7-δ (YBCO) thin films. The heterojunctions were formed in situ by sequentially growing LCMO and YBCO films on 〈100〉 LaAlO3 (LAO) substrate using a pulsed laser deposition (PLD) system. YBCO micro-bridges with 64 μm width were patterned both on
the LAO (control) and LCMO side of the substrate. Critical current, I
c, was measured at 77 K on both the control side as well as the LCMO side for different YBCO film thickness. It was observed
that while the control side showed a J
c of ∼ 2 × 106 A/cm2, the LCMO side showed about half the value for the same thickness (1800 ?). The difference in J
c indicates that a certain thickness of YBCO has become ‘effectively’ normal due to self-injection. From the measurement of
J
c at two different thicknesses (1800 ? and 1500 ?) of YBCO films both on the LAO as well as the LCMO side, the value of self-injection
length (at 77 K) was estimated to be ∼ 900 ?. To the authors’ best knowledge, this is the first time that self-injection length
has been quantified. A control experiment carried out with LaNiO3 deposited by PLD on YBCO did not show any evidence of self-injection. 相似文献
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A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling 下载免费PDF全文
Dr. Prem N. Basa Sagar Antala Prof. Dr. Robert E. Dempski Prof. Dr. Shawn C. Burdette 《Angewandte Chemie (International ed. in English)》2015,54(44):13027-13031
Metal ion signaling in biology has been studied extensively with ortho‐nitrobenzyl photocages; however, the low quantum yields and other optical properties are not ideal for these applications. We describe the synthesis and characterization of NTAdeCage, the first member in a new class of Zn2+ photocages that utilizes a light‐driven decarboxylation reaction in the metal ion release mechanism. NTAdeCage binds Zn2+ with sub‐pM affinity using a modified nitrilotriacetate chelator and exhibits an almost 6 order of magnitude decrease in metal binding affinity upon uncaging. In contrast to other metal ion photocages, NTAdeCage and the corresponding Zn2+ complex undergo efficient photolysis with quantum yields approaching 30 %. The ability of NTAdeCage to mediate the uptake of 65Zn2+ by Xenopus laevis oocytes expressing hZIP4 demonstrates the viability of this photocaging strategy to execute biological assays. 相似文献
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Mbatia HW Ulloa OA Kennedy DP Incarvito CD Burdette SC 《Organic & biomolecular chemistry》2011,9(8):2987-2991
A highly crystalline iodinating reagent, {[K·18-C-6]ICl(2)}(n), was synthesized in high yield (93%). The trihalide is supported by an 18-crown-6 macrocycle and forms a coordination polymer in the solid state. This reagent iodinates anilines and phenols efficiently under mild conditions. Controlled mono-iodination with anilines was easily achieved while poly-iodination was observed with phenols. 相似文献
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Timothy R. Totsch Victoria L. Stanford Oleksander Klep Mary K. Burdette Benjamin Grant Stephen H. Foulger Gary M. Gray 《Journal of polymer science. Part A, Polymer chemistry》2020,58(13):1825-1842
Linear polyphosphonates with the generic formula –[P(Ph)(X)OR′O]n– (X = S or Se) have been synthesized by polycondensations of P(Ph)(NEt2)2 and a diol (HOR′OH = 1,4-cyclohexanedimethanol, 1,4-benzenedimethanol, tetraethylene glycol, or 1,12-dodecanediol) followed by reaction with a chalcogen. Random copolymers have been synthesized by polycondensations of P(Ph)(NEt2)2 and mixture of two of the diols in a 2:1:1 mol ratio followed by reaction with a chalcogen. Block copolymers with the generic formula –[P(Ph)(X)OR′O](x + 2) –[P(Ph)(X)OR′O](x + 3)– (X = S or Se) have been synthesized by the polycondensations of Et2N[P(Ph)(X)OR′O](x + 2)P(Ph)NEt2 oligomers with HOR′O[P(Ph)(X)OR′O](x + 3)H oligomers followed by reaction with a chalcogen. The Et2N[P(Ph)(X)OR′O](x + 2)P(Ph)NEt2 oligomers are prepared by the reaction of an excess of P(Ph)(NEt2)2 with a diol while the HOR′O[P(Ph)(X)OR′O](x + 3)H oligomers are prepared by the reaction of P(Ph)(NEt2)2 with an excess of the diol. In each case the excess, x is the same and determines the average block sizes. All of the polymers were characterized using 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, TGA, DSC, and SEC. 31P{1H} NMR spectroscopy demonstrates that the random and block copolymers have the expected arrangements of monomers and, in the case of block copolymers, verifies the block sizes. All polymers are thermally stable up to ~300°C, and the arrangements of monomers in the copolymers (block vs. random) affect their degradation temperatures and Tg profiles. The polymers have weight average MWs of up to 3.8 × 104 Da. 相似文献
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Yulin Ren Sijin Wu Sijie Chen Joanna E. Burdette Xiaolin Cheng A. Douglas Kinghorn 《Molecules (Basel, Switzerland)》2021,26(18)
Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na+/K+-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein–protein interactions, Na+/K+-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents. 相似文献
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Fluorescent sensors for Zn(2+) based on a fluorescein platform: synthesis, properties and intracellular distribution 总被引:7,自引:0,他引:7
Burdette SC Walkup GK Spingler B Tsien RY Lippard SJ 《Journal of the American Chemical Society》2001,123(32):7831-7841
Two new fluorescent sensors for Zn(2+) that utilize fluorescein as a reporting group, Zinpyr-1 and Zinpyr-2, have been synthesized and characterized. Zinpyr-1 is prepared in one step via a Mannich reaction, and Zinpyr-2 is obtained in a multistep synthesis that utilizes 4',5'-fluorescein dicarboxaldehyde as a key intermediate. Both Zinpyr sensors have excitation and emission wavelengths in the visible range ( approximately 500 nm), dissociation constants (K(d1)) for Zn(2+) of <1 nM, quantum yields approaching unity (Phi = approximately 0.9), and cell permeability, making them well-suited for intracellular applications. A 3- to 5-fold fluorescent enhancement is observed under simulated physiological conditions corresponding to the binding of the Zn(2+) cation to the sensor, which inhibits a photoinduced electron transfer (PET) quenching pathway. The X-ray crystal structure of a 2:1 Zn(2+):Zinpyr-1 complex has also been solved, and is the first structurally characterized example of a complex of fluorescein substituted with metal binding ligands. 相似文献
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Burdette SC Frederickson CJ Bu W Lippard SJ 《Journal of the American Chemical Society》2003,125(7):1778-1787
A second-generation fluorescent sensor for Zn(2+) from the Zinpyr family, ZP4, has been synthesized and characterized. ZP4 (Zinpyr-4, 9-(o-carboxyphenyl)-2-chloro-5-[2-(bis(2-pyridylmethyl)aminomethyl)-N-methylaniline]-6-hydroxy-3-xanthanone) is prepared via a convergent synthetic strategy developed from previous studies with these compounds. ZP4, like its predecessors, has excitation and emission wavelengths in the visible range ( approximately 500 nm), a dissociation constant (K(d)) for Zn(2+) of less than 1 nM and a high quantum yields (Phi = approximately 0.4), making it well suited for biological applications. A 5-fold fluorescent enhancement is observed under simulated physiological conditions corresponding to the binding of the Zn(2+) cation to the sensor, which inhibits a photoinduced electron transfer (PET) quenching pathway. The metal-binding stereochemistry of ZP4 was evaluated through the synthesis and X-ray structural characterization of [M(BPAMP)(H(2)O)(n)](+) complexes, where BPAMP is [2-(bis(2-pyridylmethyl)aminomethyl)-N-methylaniline]-phenol and M = Mn(2+), Zn(2+) (n = 1) or Cu(2+) (n = 0). 相似文献