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1.
Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells. 总被引:35,自引:11,他引:24 下载免费PDF全文
A Zantema P I Schrier A Davis-Olivier T van Laar R T Vaessen A J van der EB 《Molecular and cellular biology》1985,5(11):3084-3091
The distribution and stability of the cellular tumor antigen p53 were studied in baby rat kidney cells transformed by region E1 sequences of nononcogenic adenovirus (Ad) type 5 (Ad5) or oncogenic type 12 (Ad12). In transformed cells expressing the large E1B T antigen of Ad5, p53 was associated with this T antigen. The complexed proteins were concentrated in a cytoplasmic body, which has been shown to consist of a cluster of 8-nm filaments (A. Zantema et al., Virology 142:44-58, 1985). In transformed cells expressing the E1B region of Ad12, however, no association between the viral large T antigen and p53 was detectable. In the latter case, both proteins were found almost exclusively in the nucleus. The stability of p53 in both Ad5- and Ad12-transformed cells was increased relative to that in primary cells or cells immortalized by the E1A region only. Thus, the increased stability of p53 in Ad-transformed cells is not caused by association with a viral T antigen, but it correlates with expression of E1B and with morphological transformation. 相似文献
2.
Swati P. Mercer Anthony J. Roecker Susan Garson Duane R. Reiss C. Meacham Harrell Kathy L. Murphy Joseph G. Bruno Rodney A. Bednar Wei Lemaire Donghui Cui Tamara D. Cabalu Cuyue Tang Thomayant Prueksaritanont George D. Hartman Steven D. Young Christopher J. Winrow John J. Renger Paul J. Coleman 《Bioorganic & medicinal chemistry letters》2013,23(24):6620-6624
The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats. 相似文献
3.
Roberto?H?Higa Roberto?C?Togawa Arnaldo?J?Montagner Juliana?CF?Palandrani Igor?KS?Okimoto Paula?R?Kuser Michel?EB?Yamagishi Adauto?L?Mancini Goran?NeshichEmail author 《BMC bioinformatics》2004,5(1):107
Background
The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. 相似文献4.
Downes M Verdecia MA Roecker AJ Hughes R Hogenesch JB Kast-Woelbern HR Bowman ME Ferrer JL Anisfeld AM Edwards PA Rosenfeld JM Alvarez JG Noel JP Nicolaou KC Evans RM 《Molecular cell》2003,11(4):1079-1092
The farnesoid X receptor (FXR) functions as a bile acid (BA) sensor coordinating cholesterol metabolism, lipid homeostasis, and absorption of dietary fats and vitamins. However, BAs are poor reagents for characterizing FXR functions due to multiple receptor independent properties. Accordingly, using combinatorial chemistry we evolved a small molecule agonist termed fexaramine with 100-fold increased affinity relative to natural compounds. Gene-profiling experiments conducted in hepatocytes with FXR-specific fexaramine versus the primary BA chenodeoxycholic acid (CDCA) produced remarkably distinct genomic targets. Highly diffracting cocrystals (1.78 A) of fexaramine bound to the ligand binding domain of FXR revealed the agonist sequestered in a 726 A(3) hydrophobic cavity and suggest a mechanistic basis for the initial step in the BA signaling pathway. The discovery of fexaramine will allow us to unravel the FXR genetic network from the BA network and selectively manipulate components of the cholesterol pathway that may be useful in treating cholesterol-related human diseases. 相似文献
5.
P. MALLE M. VALLÉ P. DEMARQUE P. EB R. TAILLIEZ 《Journal of Rapid Methods and Automation in Microbiology》1998,6(2):93-102
H2 S+ bacteria responsible for the degradation of sulfur-containing amino acids of fish muscle are currently little used to evaluate the microbiological pal quality of fish. Shewanella putrefaciens greatly predominates in this flora, and was therefore used to define a suitable culture method and medium. Inoculations by the Spiral surface method at 25C, with an incubation of 72h, gave the best counts on a medium containing two sources of sulfur (organic and inorganic) for H2 S+ bacteria. The culture medium and the NaCl concentration were determinant in the evaluation of this flora. At present there is no standard medium which meets these requirements. 相似文献
6.
Jason W. Skudlarek Christina N. DiMarco Kerim Babaoglu Anthony J. Roecker Joseph G. Bruno Mark A. Pausch Julie A. OBrien Tamara D. Cabalu Joanne Stevens Joseph Brunner Pamela L. Tannenbaum W. Peter Wuelfing Susan L. Garson Steven V. Fox Alan T. Savitz Charles M. Harrell Anthony L. Gotter Christopher J. Winrow Paul J. Coleman 《Bioorganic & medicinal chemistry letters》2017,27(6):1364-1370
In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX2R subtype and culminating in the discovery of 23, a highly potent, OX2R-selective molecule that exhibited a promising in vivo profile. Further structural modification led to an unexpected restoration of OX1R antagonism. Herein, these changes are discussed and a rationale for selectivity based on computational modeling is proposed. 相似文献
7.
Bergman JM Roecker AJ Mercer SP Bednar RA Reiss DR Ransom RW Meacham Harrell C Pettibone DJ Lemaire W Murphy KL Li C Prueksaritanont T Winrow CJ Renger JJ Koblan KS Hartman GD Coleman PJ 《Bioorganic & medicinal chemistry letters》2008,18(4):1425-1430
A series of OX(2)R/OX(1)R dual orexin antagonists was prepared based on a proline bis-amide identified as a screening lead. Through a combination of classical and library synthesis, potency enhancing replacements for both amide portions were discovered. N-methylation of the benzimidazole moiety within the lead structure significantly reduced P-gp susceptibility while increasing potency, giving rise to good brain penetration. A compound from this series has demonstrated in vivo central activity when dosed peripherally in a pharmacodynamic model of orexin activity. 相似文献
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SANDRINE BESSOU JEAN-ETIENNE SURLVE-BAZEILLE EVELYNE SORBIER ALAIN TAÏEB 《Pigment cell & melanoma research》1995,8(5):241-249
To study pigmentation, we have reconstructed an epidermis ex vivo with keratinocytes and melanocytes. Keratinocytes and melanocytes were grown first in primary cocultures and separately in secondary cultures, then seeded on a dead deepidermized dermis (Pruniéras type) at a 1:20 melanocyte/keratinocyte ratio. Reconstructed epidermis were grown in a special medium enriched with calcium and fetal bovine serum lifted for 15 days at the air-liquid interface. Using histology, immunohistochemistry and electron microscopy we have shown an excellent level of differentiation of the reconstructed epidermis and a physiologic distribution of dendritic melanocytes in the basal layer capable of melanosome transfer to keratinocytes. UVB irradiation 0.15 J/cm2× 5 consecutive days increased melanocyte numbers and stimulated pigmentation as evidenced macroscopically and microscopically and at the biochemical level. Following UVB irradiation melanosome transfer was markedly increased and isolated or clumps of melanosomes were seen in the basal layers as well as in the stratum corneum. This model allows the study of the physiology of pigmentation ex vivo. 相似文献
10.
JOZEF BIZIK SANDRINE BESSOU DIANA FELNEROVA ANTTI VAHERI ALAIN TAÏEB 《Pigment cell & melanoma research》1996,9(5):255-264
To understand the contribution of epidermal melanocytes in the proteolytic potential of human skin, we have studied melanocytes grown in a low-serum medium deprived of phorbol esters, cholera toxin, and other non-physiological supplements. We focused on the plasminogen activation system and certain matrix metalloproteinases (gelatinases). Supposing that the proteolytic activity of cells can influence binding to collagen matrix and its reorganization, we have analyzed these parameters as well. We found that human melanocytes secreted tissue-type plasminogen activator and utilised it to generate cell-bound plasmin. No urokinase-type plasminogen activator was detected in the cultures but its receptor was found in cell extracts. Both the 72 kDa and 92 kDa gelatinases were secreted by the cells and in equal amounts. In addition, melanocytes secreted the wide-spectrum proteinase inhibitor alpha-2-macroglobulin. Melanocytes cast into collagen matrices retained a rounded morphology, did not extend processes, and were unable to contract collagen lattices. As a control, these parameters were investigated in parallel in cultures of human keratinocytes, dermal fibroblasts, and two melanoma cell lines. The obtained characteristics suggest that normal human melanocytes are proteolytically active cells. This function may pertain to skin physiology and pathophysiology. 相似文献