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411.
Filzen GF Bratton L Cheng XM Erasga N Geyer A Lee C Lu G Pulaski J Sorenson RJ Unangst PC Trivedi BK Xu X 《Bioorganic & medicinal chemistry letters》2007,17(13):3630-3635
Recent literature has suggested the benefit of selective PPARdelta agonists for the treatment of atherosclerosis and other disease states associated with the metabolic syndrome. Herein we report the synthesis and structure-activity relationships of a series of novel and selective PPARdelta agonists. Our search began with identification of a novel benzothiophene template which was modified by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties. Further elucidation of the SAR led to the identification of benzofuran and indole based templates. During the course of our research, we discovered three new chemical templates with varying degrees of affinity and potency for PPARdelta versus the PPARalpha and PPARgamma subtypes. 相似文献
412.
Bratton LD Filzen GF Geyer A Hoffman JK Lu G Pulaski J Trivedi BK Unangst PC Xu X 《Bioorganic & medicinal chemistry letters》2007,17(13):3624-3629
A series of 1,4-benzyloxybenzylsulfanylaryl carboxylic acids were prepared and their activities for PPAR receptor subtypes (alpha, delta, and gamma) with potential indications for the treatment of dyslipidemia were investigated. Analog 13a displayed the greatest binding affinity (IC(50)=10nM) and selectivity (120-fold) for PPARdelta over PPARalpha. Many of the analogs investigated were found to be highly selective for PPARdelta and were dependent on the point of attachment of the substituent. In the 1,4-series, analog 28e was found to be the most potent (IC(50)=1.7 nM) and selective (>1000-fold) compound for PPARdelta. None of the compounds tested showed appreciable binding affinity for PPARgamma. 相似文献
413.
The reaction of CuCl2 · 2H2O with 2,6-bis(1-phenyliminoethyl)pyridine (referred hereafter as L) in 1:1 molar ratio in methanol or acetronitrile at room temperature afforded distorted trigonal-bipyramidal complex [Cu(κ3-L)Cl2]. On the other hand, the reaction of NiCl2 · 6H2O with 2 equivalents of L gave an octahedral complex [Ni(κ3-L)2]2+, which was isolated as [Ni(κ3-L)2][BF4]2 using NH4BF4. The complexes have been characterized by elemental analyses, FAB-MS, IR, EPR and electronic spectral studies. Molecular structures of both the [Cu(κ3-L)Cl2] (1) and [Ni(κ3-L)2](BF4)2 (2) have been determined by single crystal X-ray analyses. Weak interaction studies on 1 and 2 revealed stabilisation of the crystal packing by inter and intra-molecular C-H?X (X = F, Cl, π) interactions. In complex 2 ortho C-H bond from phenyl rings leads to unexpected C-H?π interaction with nickel α,α′-diimine chelate ring. This provides structural support for metalloaromaticity in the chelate ring of complex 2. 相似文献
414.
Yindong Xu C. L. Greenstock A. Trivedi R. E. J. Mitchel 《Radiation and environmental biophysics》1996,35(2):89-93
Interleukin-2 (IL-2) is a cytokine responsible for a variety of immune and non-immune stimulatory and regulatory functions,
including the activation and stimulation of cytotoxic cells able to recognize and kill human tumour cells and T-cell proliferation
and differentiation. We show that low doses of radiation, in the range commonly received by atomic radiation workers or as
a result of minor medical diagnostic procedures (0.25 to 10 mGy), stimulate the expression of IL-2 receptors (IL-2R) on the
surface of peripheral blood lymphocytes (PBL) taken from normal human donors. This stimulated surface expression after in
vitro irradiation is an indirect effect, resulting from the secretion into the medium of a soluble factor from the irradiated
cells. This factor can also stimulate IL-2R surface expression in unirradiated cells. Consequently, radiation stimulation
of IL-2R expression in a large population of PBL shows a triggered-type response rather than being proportional to dose. These
results demonstrate that normal human cells can respond to doses of radiation in the range of common occupational or medical
exposures. The data also demonstrate a possible defence mechanism against environmental stress by which a radiation-exposed
cell can use an indirect signalling mechanism to communicate with and influence the biological processes in an unexposed cell. 相似文献
415.
Sanjay S. Ingle Nidhi Trivedi Rakesh Prasad Jes Kuruvilla Koteshwara Kukatla Rao H.S. Chhatpar 《Current microbiology》2001,43(4):255-259
Brush border membrane vesicles (BBMVs) were prepared from the 2nd instar larvae of Helicoverpa armigera. Binding of the activated Cry1Ac of Bacillus thuringiensis (Bt) toxin was shown by immunoblot. A 120-kDa protein was identified as a receptor for the Cry1Ac type δ-endotoxin. The aminopeptidase-N
activity of BBMVs was measured as the hydrolysis of L-leucine p-nitroanilide. The specific activity was 35 units/mg protein. The BBMV preparation also showed low level of alkaline phosphatase
activity. Zn++ chelating agents 2,2′-dipyridyl and 1,10-phenanthroline inhibited aminopeptidase activity at 10 mM concentration, indicating the presence of zinc-dependent aminopeptidase in the brush border of H. armigera. The aminopeptidase activity was increased with increasing concentration of δ-endotoxin. The purified 120-kDa binding protein
was N-terminally sequenced. The first 10-amino-acid sequence showed 60–77% similarity with human cysteine-rich secretory protein-1
precursor, inhibin alpha chain precursor. Salmonella flagellar hook protein and yeast carboxypeptidase S.
Received: 4 January 2001 / Accepted: 6 February 2001 相似文献
416.
417.
Importance of the 10-13 region of glucagon for its receptor interactions and activation of adenylate cyclase 总被引:1,自引:0,他引:1
The role of the Tyr10-Ser11-Lys12-Tyr13 region of glucagon in the binding interaction and activation of the glucagon receptor was investigated by means of the synthetic glucagon analogues [Phe13]glucagonamide, [Phe10]glucagonamide, [Phe10]glucagon, [Phe10,13]glucagon, [Pro11]glucagon, [Pro11,Gly12]glucagonamide, [Ala11]glucagon, and [Oac11-13]glucagonamide. These analogues were synthesized by solid-phase peptide synthesis on p-methylbenzhydrylamine or Merrifield resins with protected N alpha-tert-butyloxycarbonyl amino acids. Purification by dialysis, cation-exchange chromatography, gel filtration, and preparative reverse-phase high-performance liquid chromatography (HPLC) gave products that proved homogeneous by thin-layer chromatography and HPLC and on analysis by amino acid analysis, by sequencing, and by alpha-chymotryptic peptide mapping with HPLC. Biological activities were examined by measurement of the stimulation of liver plasma membrane adenylate cyclase and by specific displacement of [125I]glucagon from glucagon receptors. The results of these studies indicate that while the biological "message" region of glucagon is located elsewhere, the 10-13 region has multiple roles in the glucagon-glucagon receptor interaction: this region provides functional groups for direct binding interaction with the receptor, and this region interacts with the receptor in such a way as to allow the "transduction message" portion of glucagon to interact and activate the receptor. 相似文献
418.
Importance of the C-terminal alpha-helical structure for glucagon's biological activity 总被引:1,自引:0,他引:1
J L Krstenansky C Zechel D Trivedi V J Hruby 《International journal of peptide and protein research》1988,32(6):468-475
The synthetic glucagon analogues [Glu21]glucagon, 2, and [Lys17,18,Glu21]glucagon, 3, were designed using Chou-Fasman calculations for the purpose of enhancing the probability for the formation of a C-terminal amphipathic alpha-helical conformation. Circular dichroism indicates increased alpha-helical content for these analogues in solution relative to glucagon. Analogues 2 and 3 also exhibit a 3-fold and 5-fold increase in receptor binding potency, respectively. The adenylate cyclase stimulating potencies of 2 and 3 relative to glucagon are 2.1 and 7 times greater, respectively. Attempts were made at further alpha-helical enhancement by further substitutions in the 10-13 region of glucagon, as represented by the glucagon analogues [Phe13,Lys17,18 Glu21]glucagon, 4, and [Phe10,13,Lys17,18,Glu21]glucagon, 5. These latter substitutions resulted in lowered receptor binding and adenylate cyclase potencies for 4 and 5 relative to 3 despite increased alpha-helical content in solution as observed by circular dichroism spectroscopy. 相似文献
419.
Production of extracellular cellulase by an isolate of a Fusarium sp. has been studied in shake cultures, and sequential appearance of cellulase components (- glucosidase on the first day, endo--glucanase on second day and exo--glucanase on the third day of growth on insoluble cellulose) was observed. Maximum production of all these components was achieved on the fifth day. The Fusarium produced significantly higher -glucosidase within a short period of time as compared with Trichoderma reesei. The influence of different nitrogen and carbon sources on cellulase has been investigated. Crude cellulolytic enzyme was used for hydrolysis of common agricultural wastes both with and without sodium hydroxide pretreatment. Analysis of hydrolysates indicated glucose as the major constituent (about 83% of total reducing sugar). 相似文献
420.
M. S. Srinivasa Reddy Prabodh K. Trivedi Rakesh Tuli Prafullachandra V. Sane 《Journal of genetics》1998,77(2-3):77-83
We report the cloning and nucleotide sequence analysis ofpsbD/C operon from a dicotyledonous tree species,Populus deltoides (poplar). The coding regions ofpsbD andpsbC and deduced amino acid sequences show very high homology with those from other higher plants. In pairwise alignment of the gene sequences,P. deltoides clustered with dicotyledonous annuals rather than withPinus, the only other tree whosepsbD/C nucleotide sequence is available. Comparison of several reported sequences showed that synonymous substitutions were distributed in bothpsbD andpsbC uniformly, throughout the length of the genes. The frequency of nonsynonymous substitutions located in the amino-terminal endof psbD was distinctly higher, suggesting a lower degree of structural constraints in this region of the encoded D2 protein. The arrangement of reading frames and Northern analysis suggest that organization and expression ofpsbD/C operon inP. deltoides is similar to that in other higher plants. 相似文献