排序方式: 共有89条查询结果,搜索用时 15 毫秒
1.
A new lignan glycoside, 1,5-dihydroxy-2-(4"-beta-D-glucopyranosyloxy-3"-methoxyphenyl)-6-(4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, named ambrosidine ([structure: see text]), along with seven known compounds (four iridoids and three hydroxycinnamic esters) were isolated from the roots of Cephalaria ambrosioides. The structures of these compounds were determined by use of NMR and MS techniques and by chemical transformations. The cytotoxic activity of the novel compound [structure: see text] was evaluated against five human solid tumour cell lines. 相似文献
2.
Oligonucleotides modified by a 2′-deoxy-2′-(N-methoxyamino) ribonucleotide react readily with aldehydes in slightly acidic conditions to yield the corresponding N-(methoxy)oxazolidine-linked oligonucleotide-conjugates. The reaction is reversible and dynamic in slightly acidic conditions, while the products are virtually stable above pH 7, where the reaction is in a ‘‘switched off-state’’. Small molecular examinations have demonstrated that aldehyde constituents affect the cleavage rate of the N-(methoxy)oxazolidine-linkage. This can be utilized to adjust the stability of this pH-responsive cleavable linker for drug delivery applications. In the present study, Fmoc-β-Ala-H was immobilized to a serine-modified ChemMatrix resin and used for the automated assembly of two peptidealdehydes and one aldehyde-modified peptide nucleic acid (PNA). In addition, a triantennary N-acetyl-d-galactosamine-cluster with a β-Ala-H unit has been synthesized. These aldehydes were conjugated via N-(methoxy)oxazolidine-linkage to therapeutically relevant oligonucleotide phosphorothioates and one DNA-aptamer in 19–47% isolated yields. The cleavage rates of the conjugates were studied in slightly acidic conditions. In addition to the diverse set of conjugates synthesized, these experiments and a comparison to published data demonstrate that the simple conversion of Gly-H to β-Ala-H residue resulted in a faster cleavage of the N-(methoxy)oxazolidine-linker at pH 5, being comparable (T0.5 ca 7 h) to hydrazone-based structures. 相似文献
3.
Mendoza SM Whelan CM Jalkanen JP Zerbetto F Gatti FG Kay ER Leigh DA Lubomska M Rudolf P 《The Journal of chemical physics》2005,123(24):244708
Thin films of fumaramide [2]rotaxane, a mechanically interlocked molecule composed of a macrocycle and a thread in a "bead and thread" configuration, were prepared by vapor deposition on both Ag(111) and Au(111) substrates. X-ray photoelectron spectroscopy (XPS) and high-resolution electron-energy-loss spectroscopy were used to characterize monolayer and bulklike multilayer films. XPS determination of the relative amounts of carbon, nitrogen, and oxygen indicates that the molecule adsorbs intact. On both metal surfaces, molecules in the first adsorbed layer show an additional component in the C 1s XPS line attributed to chemisorption via amide groups. Molecular-dynamics simulation indicates that the molecule orients two of its eight phenyl rings, one from the macrocycle and one from the thread, in a parallel bonding geometry with respect to the metal surfaces, leaving three amide groups very close to the substrate. In the case of fumaramide [2]rotaxane adsorption on Au(111), the presence of certain out-of-plane phenyl ring and Au-O vibrational modes points to such bonding and a preferential molecular orientation. The theoretical and experimental results imply that the three-dimensional intermolecular configuration permits chemisorption at low coverage to be driven by interactions between the three amide functions of fumaramide [2]rotaxane and the Ag(111) or Au(111) surface. 相似文献
4.
K. J. Jalkanen Julian D. Gale P. R. Lassen L. Hemmingsen A. Rodarte I. M. Degtyarenko R. M. Nieminen S. Brøgger Christensen M. Knapp-Mohammady S. Suhai 《Theoretical chemistry accounts》2008,119(1-3):177-190
In this work we present the experimental and theoretical vibrational absorption (VA) and the theoretical vibrational circular
dichroism (VCD) spectra for aframodial. In addition, we present the theoretical VA and VCD spectra for the diasteriomers of
aframodial. Aframodial has four chiral centers and hence has 24 = 16 diasteriomers, which occur in eight pairs of enantiomers. In addition to the four chiral centers, there is an additional
chirality due to the helicity of the entire molecule, which we show by presenting 12 configurations of the 5S,8S,9R,10S enantiomer
of aframodial. The VCD spectra for the diasteriomers and the 12 configurations of one enantiomer are shown to be very sensitive
not only to the local stereochemistry at each chiral center, but in addition, to the helicity of the entire molecule. Here
one must be careful in analyzing the signs of the VCD bands due to the ‘non-chiral’ chromophores in the molecule, since one
has two contributions; one due to the inherent chirality at the four chiral centers, and one due to the chirality of the side
chain groups in specific conformers, that is, its helicity. Theoretical simulations for various levels of theory are compared
to the experimental VA recorded to date. The VCD spectra simulations are presented, but no experimental VCD and Raman spectra
have been reported to date, though some preliminary VCD measurements have been made in Stephens’ lab in Los Angeles. The flexible
side chain is proposed to be responsible for the small size of the VCD spectra of this molecule, even though the chiral part
of the molecule is very rigid and has four chiral centers. In addition to VCD and Raman measurements, Raman optical activity
(ROA) measurements would be very enlightening, as in many cases bands which are weak in both the VA and VCD, may be large
in the Raman and/or ROA spectra. The feasibility of using vibrational spectroscopy to monitor biological structure, function
and activity is a worthy goal, but this work shows that a careful theoretical analysis is also required, if one is to fully
utilize and understand the experimental results. The reliability, reproduceability and uniqueness of the vibrational spectroscopic
experiments and the information which can be gained from them is discussed, as well as the details of the computation of VA,
VCD and Raman (and ROA) spectroscopy for molecules of the complexity of aframodial, which have multiple chiral centers and
flexible side chains.
Festschrift in Honor of Philip J. Stephens’ 65th Birthday. 相似文献
5.
Dr. Jaebong Jang Dr. Ciric To Dr. Dries J. H. De Clercq Dr. Eunyoung Park Charles M. Ponthier Bo Hee Shin Mierzhati Mushajiang Dr. Radosław P. Nowak Dr. Eric S. Fischer Dr. Michael J. Eck Dr. Pasi A. Jänne Dr. Nathanael S. Gray 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(34):14589-14597
Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug-resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced. Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP-site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR. 相似文献
6.
Straightforward synthesis for two pentaerythrityltetramine precursors, 2,2-bis(azidomethyl)propane-1,3-diamine (1) and 2-[N-(allyloxycarbonyl)aminomethyl]-2-azidomethylpropane-1,3-diamine (2), has been described. Both propane-1,3-diamines have been attached by reductive amination to a solid-supported backbone amide linker derived from 4-(4-formyl-3,5-dimethoxyphenoxy)butyric acid. The presence of the two methoxy substituents on the linker is essential to avoid cross-linking between two linkers. The remaining free primary amino group of the propane-1,3-diamine moiety may then be selectively acylated with an appropriately protected amino acid using conventional N,N-dicyclohexylcarbodiimide/1-hydroxybenzotriazole (DCC/HOBt) activation without any interference by the secondary amino function. The latter group may be subsequently acylated by an anhydride method. Sequential reduction of the azido group and removal of the allyloxycarbonyl protection from 2 allow further coupling of two different amino acids, and hence, this handle may be utilized in construction of branched structures containing four different amino acids or peptides. Solid-supported 1 may, in turn, be used for the synthesis of similar constructs containing two identical branches. It is worth noting that no acid-labile protecting groups are required in this approach, and hence, this dimension may be saved for the cleavage of the linker. The applicability of the scaffolds to library synthesis has been demonstrated by preparation of 11 pentaerythrityl-branched tetra- and octapeptides. 相似文献
7.
Mika Tiainen Hannu Maaheimo Pasi Soininen Reino Laatikainen 《Magnetic resonance in chemistry : MRC》2010,48(2):117-122
The one‐ and two‐bond 13C isotope shifts, typically ?1.5 to ?2.5 ppb and ?0.7 ppb respectively, in non‐cyclic aliphatic systems and up to ?4.4 ppb and ?1.0 ppb in glucose cause effects that need to be taken into account in the adaptive NMR spectral library‐based quantification of the isotopomer mixtures. In this work, NMR spectral analyses of some 13C‐labelled amino acids, D ‐glucose and other small compounds were performed in order to obtain rules for prediction of the 13C isotope effects on 1H chemical shifts. It is proposed that using the additivity rules, the isotope effects can be predicted with a sufficient accuracy for amino acid isotopomer applications. For glucose the effects were found strongly non‐additive. The complete spectral analysis of fully 13C‐labelled D ‐glucose made it also possible to assign the exocyclic proton signals of the glucose. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
8.
Ville Nieminen Markus Karjalainen Katri Salminen Jussi Rantala Anton Kontunen Poika Isokoski Philipp Müller Pasi Kallio Veikko Surakka Jukka Lekkala 《International Journal for Ion Mobility Spectrometry》2018,21(3):71-80
Production of easily controllable and measurable odor stimuli is needed when studying human olfaction, olfaction-related physiology and psychological reactions to odors. Controlled odor producing instruments are called olfactometers. For testing and calibrating new olfactometers or sensor arrays, a reliable input signal has to be produced to verify their accurate functionality. A common input signal in various olfactometers has been the use of volatile organic compounds (VOCs) in gaseous form. We present a compact olfactometer able to produce controlled continuous odor stimuli from three individual channels. For measuring the output gas flow, we used a ChemPro 100i (Environics, Finland) device that is based on aspiration ion mobility spectrometry (aIMS). IMS is a robust and sensitive method for measuring VOCs and is used especially in detecting toxic industrial chemicals and chemical warfare agents, but the technology is also suitable for other olfactory-related applications. The olfactometer was used to produce synthetic jasmine scent using three main odor components from jasmine oil and all the components were diluted using propylene glycol. The dilutions were supplied to the system using programmable syringe pumps, which guided the dilutions to individual evaporation units. We conducted experiments to verify the functionality of our olfactometer. Analysis of the ChemPro100i data showed that olfactometer can use different odor components to produce continuous, stable output flows with controlled concentrations. 相似文献
9.
Lombardo M Easwar S De Marco A Pasi F Trombini C 《Organic & biomolecular chemistry》2008,6(22):4224-4229
Catalyst 5, an ion pair consisting of a hydrophilic cation and a lipophilic anion, fulfils the solubility requirements needed to couple efficiency (enantioselectivities and anti-diastereoselectivities up to > or = 99%) and catalyst recyclability in asymmetric aldol reactions under aqueous biphasic conditions. 相似文献
10.
Peeters M Verschaffelt G Speybrouck J Thienpont H Danckaert J Turunen J Vahimaa P 《Optics letters》2006,31(9):1178-1180
Recently we observed a strong reduction of spatial coherence of the emission of large-aperture vertical-cavity surface-emitting lasers when they are driven by microsecond electrical pulses [Opt. Express 13, 9337 (2005)]. We study the influence of this partial spatial coherence on the propagation characteristics. The spatial decoherence manifests itself in the formation of a Gaussian far-field intensity distribution. We measure the transverse pulse profile from near to far field and see that the shape-invariant far-field regime starts after 140 microm in the pulsed regime as opposed to several centimeters in continuous wave operation. This value matches quantitatively calculations made with a novel partially coherent propagation model without any free fitting parameters. 相似文献