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821.
822.
823.
We present a novel method for on-chip cell lysis based on local hydroxide electro-generation. Hydroxide ions porate the cell membrane, leading to cell lysis. After lysis occurs, hydrogen ions, also generated on chip, react with excess hydroxide, creating a neutral pH lysate and eliminating the need for a wash step. Three different cell types are shown to be effectively lysed by this method: red blood cells, HeLa (human tumor line) and Chinese Hamster Ovary (CHO) cell lines. The release of cytoplasmic molecules from HeLa and CHO cells is demonstrated by monitoring the escape of a membrane impermeant dye from the cytoplasm. In the vicinity of the cathode, the hydroxide concentration is predicted by finite element simulations and shown to fit the lysis rates at different distances from the generating cathode. For flow-through experiments, a second device integrating a mechanical filter with hydroxide generation is fabricated and tested. The purpose of the filter is to trap whole cells and only allow lysate to pass through. The flow rate dependence of hydroxide concentration at the lysis filter is modeled and lysis efficiency is experimentally determined to be proportional to the hydroxide concentration for flow rates from 15 to 30 microl min(-1). 相似文献
824.
The isolation and structure elucidation of belamide A from the marine cyanobacterium Symploca sp. is described. Belamide A is a highly methylated linear tetrapeptide with structural analogy to the important linear peptides dolastatins 10 and 15. Disruption of the microtubule network in A-10 cells was observed at 20 μM and displayed classic tubulin destabilizing antimitotic characteristics. The moderate cytotoxicity of belamide A (IC50 0.74 μM vs HCT-116 colon cancer line) provides new insights into structure-activity relationships for this drug class. 相似文献
825.
Luke A. Burke 《International journal of quantum chemistry》1986,29(3):511-518
Defined as the formation of two new bonds of equal length at the same time, synchronism has been shown to be not possible for the Diels-Alder reaction when the products are not of strict Cs symmetry. This has been done in two steps. First, the SCF -MO transition-state structures for the cyclization reactions of ethylene with cyclopentadiene and furan have been calculated. The activation energies (and heat of reaction) with the STO -3G, 3-21G, and 4-31G basis sets are as follows: with cyclopentadiene 35.0 (?80.7), 30.0 (?32.0), 38.4 (?19.9) kcal/mol; with furan 33.4 (?66.4), 34.6 (?16.5), 42.1 (?8.8) kcal/mol. Then, using a bond-order-bond-length relationship, a value for the tendency toward asynchronism has been calculated for substituted reactants where the two new bonds are arbitrarily held equal. This tendency has been shown in all cases which break strict Cs symmetry. Further, inspection of the atomic-orbital coefficients showed that the substituents cannot be considered as mere perturbations on the pi system in many cases. 相似文献
826.
Thompson MK Doble DM Tso LS Barra S Botta M Aime S Raymond KN 《Inorganic chemistry》2004,43(26):8577-8586
The synthesis and relaxometric properties of hetero-tripodal hydroxypyridonate-terephthalamide gadolinium (Gd(3+)) chelates with differing structural features for probing human serum albumin (HSA) interactions are reported. The Gd(3+) complexes are divided into two series. The first series (3-5) features a benzyl derivative connected to the hydroxypyridonate (HOPO) moiety. The second series of complexes (6-10) has the common feature of a poly(ethylene glycol) (PEG) attached to the terephthalamide (TAM) moiety and is nonbenzylated. The water exchange of the complexes is in the fast exchange regime with rates (k(ex)) in the range 0.45-1.11 x 10(8) s(-1). The complexes have a moderate interaction with HSA with association constants (K(A)'s) in the range 0.7-8.6 x 10(3) M(-1). Protein binding results in an enhancement in proton relaxivity from 7.7-10.4 mM(-1) s(-1) (r(1p)) to 15-29 mM(-1) s(-1) (r(1p)(b)). It is concluded that the interaction of the complexes with HSA (i) is enhanced by the presence of benzyl groups, (ii) is entropically driven, and (iii) results in a lower hydration number (q). 相似文献
827.
ZHENG Yuan-zhi Luke Guddat Anthony Farlow John de Jersey 《高等学校化学研究》2006,22(2):251-252
Introduction Hypoxanthine guaninephosphoribosyltransferase(HGPRT,EC2.4.2.8)isakeyenzymeofthepurine salvagepathway,whichallowsrecyclingofpurinebases intoDNAandRNA.Itiswidelydistributedinnature andhasbeenstudiedbothinprokaryotesandeu karyotes.Inhumans,acomp… 相似文献
828.
Luke A. Adams 《Tetrahedron letters》2004,45(23):4489-4493
A versatile synthesis of the bicyclo[2.2.2]diazaoctane core structure of asperparaline, brevianamide, paraherquamide, and stephacidin natural products is demonstrated. This convergent synthesis relies on an intramolecular hetero Diels-Alder reaction to construct the key tetracycle from a diketopiperazine derived azadiene; which in turn was formed from prolinamide and a pyruvic acid derivative. The stereochemical outcome of the Diels-Alder reaction was found to favor the brevianamide stereochemistry. 相似文献
829.
Shen HC Wang J Cole KP McLaughlin MJ Morgan CD Douglas CJ Hsung RP Coverdale HA Gerasyuto AI Hahn JM Liu J Sklenicka HM Wei LL Zehnder LR Zificsak CA 《The Journal of organic chemistry》2003,68(5):1729-1735
A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of alpha,beta-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6pi-electron electrocyclic ring-closure of 1-oxatrienes. 相似文献
830.
Lisa-Maria Needham Judith Weber Juan A. Varela James W. B. Fyfe Dung T. Do Catherine K. Xu Luke Tutton Rachel Cliffe Benjamin Keenlyside David Klenerman Christopher M. Dobson Christopher A. Hunter Karin H. Müller Kevin O'Holleran Sarah E. Bohndiek Thomas N. Snaddon Steven F. Lee 《Chemical science》2020,11(18):4578
Neurodegenerative diseases such as Alzheimer''s and Parkinson''s are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, the improved optical properties (extinction coefficient, quantum yield and brightness) of ThX can be used to monitor structural differences in oligomeric species, not observed via traditional ThT imaging.Introducing ThX, a next-generation ThT derivative that allows for the early detection of amyloid aggregates at the bulk and single-aggregate levels. 相似文献