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排序方式: 共有153条查询结果,搜索用时 15 毫秒
41.
Ennis MD Hoffman RL Ghazal NB Olson RM Knauer CS Chio CL Hyslop DK Campbell JE Fitzgerald LW Nichols NF Svensson KA McCall RB Haber CL Kagey ML Dinh DM 《Bioorganic & medicinal chemistry letters》2003,13(14):2369-2372
The design and synthesis of the novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole 5 is described. This azepinoindole has excellent affinity for 5-HT(2C) (K(i) 4.8 nM) and modest selectivity over 5-HT(2A) ( approximately 4-fold). Several N- and C(11)-substituted analogues of 5 were prepared, as were a number of biaryl indoline derivatives. The anxiolytic potential for the azepinoindole template 5 is demonstrated by activity in a mouse shock-aggression assay. 相似文献
42.
Protease nexin 1 (PN1) in solution forms inhibitory complexes with thrombin or urokinase, which have opposing effects on the blood coagulation cascade. An initial report provided data supporting the idea that PN1 target protease specificity is under the influence of collagen type IV (1). Although collagen type IV demonstrated no effect on the association rate between PN1 and thrombin, the study reported that the association rate between PN1 and urokinase was allosterically reduced 10-fold. This has led to the generally accepted idea that the primary role of PN1 in the brain is to act as a rapid thrombin inhibition and clearance mechanism during trauma and loss of vascular integrity. In studies to identify the structural determinants of PN1 that mediate the allosteric interaction with collagen type IV, we found that protease specificity was only affected after transient exposure of PN1 to acidic conditions that mimic the elution protocol from a monoclonal antibody column. Because PN1 used in previous studies was purified over a monoclonal antibody column, we propose that the allosteric regulation of PN1 target protease specificity by collagen type IV is a result of the purification protocol. We provide both biochemical and kinetic data to support this conclusion. This finding is significant because it implies that PN1 may play a much larger role in the modeling and remodeling of brain tissues during development and is not simply an extravasated thrombin clearance mechanism as previously suggested. 相似文献
43.
The murid rodent subfamily Sigmodontinae contains 79 genera which are
distributed throughout the New World. The time of arrival of the first
sigmodontines in South America and the estimated divergence time(s) of the
different lineages of South American sigmodontines have been controversial
due to the lack of a good fossil record and the immense number of extant
species. The "early-arrival hypothesis" states that the sigmodontines must
have arrived in South America no later than the early Miocene, at least 20
MYA, in order to account for their vast present-day diversity, whereas the
"late-arrival hypothesis" includes the sigmodontines as part of the
Plio-Pleistocene Great American Interchange, which occurred approximately
3.5 MYA. The phylogenetic relationships among 33 of these genera were
reconstructed using mitochondrial DNA (mtDNA) sequence data from the ND3,
ND4L, arginine tRNA, and ND4 genes, which we show to be evolving at the
same rate. A molecular clock was calibrated for these genes using published
fossil dates, and the genetic distances were estimated from the DNA
sequences in this study. The molecular clock was used to estimate the dates
of the South American sigmodontine origin and the main sigmodontine
radiation in order to evaluate the "early-" and "late-arrival" scenarios.
We estimate the time of the sigmodontine invasion of South America as
between approximately 5 and 9 MYA, supporting neither of the scenarios but
suggesting two possible models in which the invading lineage was either (1)
ancestral to the oryzomyines, akodonts, and phyllotines or (2) ancestral to
the akodonts and phyllotines and accompanied by the oryzomyines. The
sigmodontine invasion of South America provides an example of the advantage
afforded to a lineage by the fortuitous invasion of a previously
unexploited habitat, in this case an entire continent.
相似文献
44.
Christina Uth Simon Englert Olga Avrutina Harald Kolmar Sascha Knauer 《Journal of peptide science》2023,29(12):e3527
We report the first application of a novel amino-Li resin to water-based solid-phase peptide synthesis (SPPS) applying the Smoc-protecting group approach. We demonstrated that it is a suitable support for the sustainable water-based alternative to a classical SPPS approach. The resin possesses good swelling properties in aqueous milieu, provides significant coupling sites, and may be applicable to the synthesis of difficult sequences and aggregation-prone peptides. 相似文献
45.
46.
A temperature sensitive mutant of Rous sarcoma virus (tsNY68) was used to obtain cultures of quiescent virus-infected chicken embryo fibroblasts arrested by serum starvation at the non-permissive temperature. Upon shift to the permissive temperature, these cells enter the replicative cell cycle as evidenced by increases in 2-deoxyglucose uptake, 3H-thymidine incorporation and percent labeled nuclei. These changes occur in the absence of serum and the cells become morphologically transformed within eight to ten hours after the temperature shift. Entry into the S phase temporally resembles that of normal quiescent fibroblasts stimulated with serum. This experimental system was used to examine the proliferative response of transformed cells to serum and purified multiplication-stimulating activity (MSA) during the transition from the resting to the growing state. Data are presented which show that the presence of serum in the medium enhances the proliferative response of quiescent infected cells shifted to the permissive temperature over those shifted in the absence of serum. In contrast, the presence of MSA has no additional effect on the response exhibited by infected cells shifted to the permissive temperature in serum-free medium. Labeled MSA binding experiments show that this lack of response is not due to a loss of MSA receptors on the cell surface since transformed cells are still capable of binding MSA at the same level as normal cells. The results are consistent with the hypothesis that the set of biochemical events initiated by MSA in normal cells are turned on in infected cells shifted to the permissive temperature by the activation of the src gene product. 相似文献
47.
Factors affecting the activity and stability of the palmitoyl-coenzyme A hydrolase of rat brain
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Thomas E. Knauer 《The Biochemical journal》1979,179(3):515-523
Palmitoyl-CoA hydrolase (EC 3.1.2.2) catalyses the irreversible hydrolysis of long-chain acyl-CoA thioesters. This enzyme is found primarily in the postmicrosomal supernatant fraction prepared from homogenates of rat brain. Either of two forms of the hydrolase, a lower-molecular-weight species of approx. 70000 or a higher-molecular-weight species of approx. 130000 can be isolated by gel filtration. The higher-molecular-weight form is obtained from columns of Sephadex G-200 eluted with buffer containing 10mum-palmitoyl-CoA or 20% (v/v) glycerol, whereas the lower-molecular-weight form is obtained when the eluting buffer does not contain palmitoyl-CoA or glycerol. The two forms of the hydrolase have the same pH optimum of 7.5, are equally sensitive to the thiol-blocking reagents p-hydroxymercuribenzoate, HgCl(2), and 5,5'-dithiobis-(2-nitrobenzoic acid), and exhibit the same K(m) (1.8mum) with palmitoyl-CoA as substrate. The two forms differ in the availability or reactivity of certain external thiol groups, as determined by covalent chromatography with activated thiol Sepharose. Dilute solutions of the lower-molecular-weight form of the hydrolase rapidly lose activity (50% in 60min at 0 degrees C), but there is no change in the K(m) with palmitoyl-CoA as substrate during this progressive inactivation. Dilutions of the hydrolase in buffer containing 10mum-palmitoyl-CoA retain full activity. However, addition of palmitoyl-CoA to solutions of the lower-molecular-weight form will not restore previously lost hydrolase activity. The evidence supports the conclusion that the substrate palmitoyl-CoA promotes the formation of a relatively stable dimer from two unstable subunits. This process may not be reversible, since the removal of palmitoyl-CoA or glycerol from solutions of the higher-molecular-weight form does not result in the appearance of the lower-molecular-weight form of the hydrolase. 相似文献
48.
Zooplankton fecal pellet fluxes and vertical transport of particulate organic material in the pelagic environment 总被引:3,自引:0,他引:3
Fecal pellet fluxes were determined using a series of multireplicatetraps set at 35, 65, 150, 500, 750 and 1500 m in the northeastPacific. Fecal pellets appear to be important contributors to total carbonfluxes. In near-surface waters (35150 m), pellet fluxesranged from 23 x 105 pellets m2 day1. Minimumpellet fluxes were observed at 500m({small tilde}0.4x 105 pelletsm2day1). In contrast, the 1500 m pellet flux valueincreased to approximately 0.8 x 105 pellets m2 day1relative to the 500 m depth, and is probably the result of insitu repackaging. Analyses of pellet content suggest multiplesources of "large" particle input throughout the water column.The implications of this phenomenon are discussed in terms ofthe detrital rain and ladder of migration theories. 相似文献
49.
The rat liver cell line, BRL-3A, is known to produce a family of polypeptides referred to as multiplication-stimulating-activity (MSA). Serum-free conditioned medium from this cell line is a rich source for the purification of these somatomedin-like molecules. Somatomedins in serum, as well as MSA produced by BRL-3A cells in culture, exist primarily as a high molecular weight complex bound to specific carrier proteins. This study describes the purification of the MSA carrier protein (MCP) from conditioned medium using affinity chromatographic procedures. The purified carrier protein is shown to specifically bind labeled MSA and generates a complex with an apparent molecular weight of 60,000–70,000 daltons. Characterization of the carrier protein indicates that it consists of two different noncovalently linked protein chains with apparent molecular weights of 30,000 and 31,500 daltons. The availability of a pure carrier protein should provide a unique opportunity to investigate the functional significance of the carrier protein in the biological activity of the somatomedins. 相似文献
50.