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1.
Wang T Frederick KK Igumenova TI Wand AJ Zuiderweg ER 《Journal of the American Chemical Society》2005,127(3):828-829
The fast dynamics of protein backbones are often investigated by nuclear magnetic relaxation experiments that report on the degree of spatial restriction of the amide bond vector. By comparing calmodulin in the peptide-bound and peptide-free states with these classical methods, we observe little difference in the dynamics of the polypeptide main chain (average order parameter decrease of 0.01 unit upon binding). However, when using NMR methods that monitor the mobility of the CO-Calpha bond vector, we reveal a significant reduction of dynamics of the protein main chain (average order parameter decrease of 0.048 units). Previous investigations have suggested that the side-chain dynamics is reduced by an average of 0.07 order parameter units upon ligand binding (Lee, A. L.; Kinnear, S. A.; Wand, A. J. Nat. Struct. Biol. 2000, 7, 72-77). The current findings suggest that the change of the CO-Calpha bond vector dynamics is intermediate between the changes in NH and side-chain dynamics and report a previously undetected loss of main-chain entropy. Weak site-to-site correlations between the different motional indicators are also observed. 相似文献
2.
November 22, 2007, marked the 25th anniversary of the National Synchrotron Light Source's (NSLS) dedication. During the last quarter-century, Brookhaven National Laboratory's NSLS has made significant contributions to the field of synchrotron radiation, ranging from the Chasman-Green Lattice, novel insertion devices, and free electron laser research, to the development of numerous synchrotron experimental techniques and instrumentation. 相似文献
3.
Rumbaugh KP 《Analytical and bioanalytical chemistry》2007,387(2):425-435
Most living organisms possess sophisticated cell-signaling networks in which lipid-based signals modulate biological effects
such as cell differentiation, reproduction and immune responses. Acyl homoserine lactone (AHL) autoinducers are fatty acid-based
signaling molecules synthesized by several Gram-negative bacteria that are used to coordinate gene expression in a process
termed “quorum sensing” (QS). Recent evidence shows that autoinducers not only control gene expression in bacterial cells,
but also alter gene expression in mammalian cells. These alterations include modulation of proinflammatory cytokines and induction
of apoptosis. Some of these responses may have deleterious effects on the host’s immune response, thereby leading to increased
bacterial pathogenesis. Prokaryotes and eukaryotes have cohabited for approximately two billion years, during which time they
have been exposed to each others’ soluble signaling molecules. We postulate that organisms from the different kingdoms of
nature have acquired mechanisms to sense and respond to each others signaling molecules, and we have named this process interkingdom
signaling. We further propose that autoinducers, which exhibit structural and functional similarities to mammalian lipid-based
hormones, are excellent candidates for mediating this interkingdom communication. Here we will compare and contrast bacterial
QS systems with eukaryotic endocrine systems, and discuss the mechanisms by which autoinducers may exploit mammalian signal
transduction pathways. 相似文献
4.
Kemal Arda Günay Tova L. Ceccato Jason S. Silver Kendra L. Bannister Olivia J. Bednarski Leslie A. Leinwand Kristi S. Anseth 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(29):10017-10021
There is a growing interest in materials that can dynamically change their properties in the presence of cells to study mechanobiology. Herein, we exploit the 365 nm light mediated [4+4] photodimerization of anthracene groups to develop cytocompatible PEG‐based hydrogels with tailorable initial moduli that can be further stiffened. A hydrogel formulation that can stiffen from 10 to 50 kPa, corresponding to the stiffness of a healthy and fibrotic heart, respectively, was prepared. This system was used to monitor the stiffness‐dependent localization of NFAT, a downstream target of intracellular calcium signaling using a reporter in live cardiac fibroblasts (CFbs). NFAT translocates to the nucleus of CFbs on stiffening hydrogels within 6 h, whereas it remains cytoplasmic when the CFbs are cultured on either 10 or 50 kPa static hydrogels. This finding demonstrates how dynamic changes in the mechanical properties of a material can reveal the kinetics of mechanoresponsive cell signaling pathways that may otherwise be missed in cells cultured on static substrates. 相似文献
5.
6.
Yuan Y Arnatt CK Li G Haney KM Ding D Jacob JC Selley DE Zhang Y 《Organic & biomolecular chemistry》2012,10(13):2633-2646
The bivalent ligand approach has been utilized not only to study the underlying mechanism of G protein-coupled receptors dimerization and/or oligomerization, but also to enhance ligand affinity and/or selectivity for potential treatment of a variety of diseases by targeting this process. Substance abuse and addiction have made both the prevention and the treatment of human immunodeficiency virus (HIV) infection more difficult to tackle. Morphine, a mu opioid receptor (MOR) agonist, can accelerate HIV infection through up-regulating the expression of the chemokine receptor CCR5, a well-known co-receptor for HIV invasion to the host cells and this has been extensively studied. Meanwhile, two research groups have described the putative MOR-CCR5 heterodimers in their independent studies. The purpose of this paper is to report the design and synthesis of a bivalent ligand to explore the biological and pharmacological process of the putative MOR-CCR5 dimerization phenomenon. The developed bivalent ligand thus contains two distinct pharmacophores linked through a spacer; ideally one of which will interact with the MOR and the other with the CCR5. Naltrexone and Maraviroc were selected as the pharmacophores to generate such a bivalent probe. The overall reaction route to prepare this bivalent ligand was convergent and efficient, and involved sixteen steps with moderate to good yields. The preliminary biological characterization showed that the bivalent compound 1 retained the pharmacological characteristics of both pharmacophores towards the MOR and the CCR5 respectively with relatively lower binding affinity, which tentatively validated our original molecular design. 相似文献
7.
The relative reactivity of building blocks is critical for a successful preparation of combinatorial libraries. Here, we present a method for measuring the reactivity of carboxylic acid building blocks in amide-forming reactions. The method involves competitive reactions between a reference and test acid and a tetraphenylporphyrin reaction partner with four reactive sites. Relative reactivities are calculated on the basis of the distribution of substituted porphyrins found in MALDI-TOF mass spectra. Reactivities thus determined were used to prepare reactivity-adjusted building block mixtures. These were reacted with amino-terminal oligonucleotide and peptide scaffolds on solid support, generating small libraries suitable for spectrometrically monitored selection experiments (SMOSE). The rate of building block "drop outs" that fail to couple as expected was not substantially lowered by acquiring spectra from two reactions, performed with different ratios of building blocks, where the effect of a given substituent on the desorption/ionization yield of the porphyrin can be eliminated. Instead, coupling building blocks of similar size together or employing N-hydroxysuccinimide esters rather than activating with a "uronium salt" were found to improve the quality of libraries generated via competitive reactions. 相似文献
8.
Kendra Killpatrick 《Journal of Combinatorial Theory, Series A》2005,110(2):337-351
Tableaux have long been used to study combinatorial properties of permutations and multiset permutations. Discovered independently by Robinson and Schensted and generalized by Knuth, the Robinson–Schensted correspondence has provided a fundamental tool for relating permutations to tableaux. In 1963, Schützenberger defined a process called evacuation on standard tableaux which gives a relationship between the pairs of tableaux (P,Q) resulting from the Schensted correspondence for a permutation and both the reverse and the complement of that permutation. Viennot gave a geometric construction for the Schensted correspondence and Fomin described a generalization of the correspondence which provides a bijection between permutations and pairs of chains in Young's lattice.In 1975, Stanley defined a Fibonacci lattice and in 1988 he introduced the idea of a differential poset. Roby gave an insertion algorithm, analogous to the Schensted correspondence, for mapping a permutation to a pair of Fibonacci tableaux. The main results of this paper are to give an evacuation algorithm for the Fibonacci tableaux that is analogous to the evacuation algorithm on Young tableaux and to describe a geometric construction for the Fibonacci tableaux that is similar to Viennot's geometric construction for Young tableaux. 相似文献
9.
High Selectivity for Ethylene from Carbon Dioxide Reduction over Copper Nanocube Electrocatalysts
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Dr. F. Sloan Roberts Dr. Kendra P. Kuhl Prof. Anders Nilsson 《Angewandte Chemie (International ed. in English)》2015,54(17):5179-5182
Nanostructured surfaces have been shown to greatly enhance the activity and selectivity of many different catalysts. Here we report a nanostructured copper surface that gives high selectivity for ethylene formation from electrocatalytic CO2 reduction. The nanostructured copper is easily formed in situ during the CO2 reduction reaction, and scanning electron microscopy (SEM) shows the surface to be dominated by cubic structures. Using online electrochemical mass spectrometry (OLEMS), the onset potentials and relative selectivity toward the volatile products (ethylene and methane) were measured for several different copper surfaces and single crystals, relating the cubic shape of the copper surface to the greatly enhanced ethylene selectivity. The ability of the cubic nanostructure to so strongly favor multicarbon product formation from CO2 reduction, and in particular ethylene over methane, is unique to this surface and is an important step toward developing a catalyst that has exclusive selectivity for multicarbon products. 相似文献
10.
Charles E. Carraher Jr. Michael R. Roner Cara Lea Carraher Ryan Crichton Kendra Black 《高分子科学杂志,A辑:纯化学与应用化学》2013,50(11):867-886
Suitable structure characterization is assisted through the use of mass spectrometry. Polymer fragmentation can be achieved in many ways including application of heat and ionizing radiation. MALDI MS allows routine analysis of polymers allowing identification of several repeat units. Graphite as a matrix allows higher mass ions to be created with less interfering ion fragments formed in comparison to more utilized matrix materials. 相似文献