共查询到20条相似文献,搜索用时 15 毫秒
1.
Tutomu Masuda Mitsuko Yoshino Izumi Nishizaki Akira Tai Hiroshi Ozaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):2199-2201
In order to elucidate the structure-activity relationship of griseofulvin (1), (±)-6′-demethyl analog (3), 2′-demethoxy-6′-demethyldihydro analog (4), (±)-dechloro-6′-ethyl analog (5), (±)-dechloro-6′-epi-ethyl analog (6), (±)-6′-ethyl analog (7) and (±)-6′-epi-ethyl analog (8) were synthesized by a Diels-Alder cycloaddition of alkylidene ketones (16, 17, 18, 19 and 20) with modified 1,3-butadienes (21 or 22). Their biological activities were examined against fungi. 相似文献
2.
Xing N L Maldonado ML Bachman LA McKean DJ Kumar R Griffin MD 《Biochemical and biophysical research communications》2002,297(3):645-652
Dendritic cell (DC) maturation plays a central role in regulating immunity. We show that glucocorticoid and 1alpha,25(OH)(2)D(3) agonists modulate DCs via distinct and additive signaling pathways. Phenotypic and functional indices were examined in DCs treated with dexamethasone (DEX) and/or a 1alpha,25(OH)(2)D(3) analog (D(3) analog). DEX potently attenuated pro-inflammatory cytokines and chemokines but had modest, reversible effects on T-cell stimulatory capacity. D(3) analog produced significantly greater inhibition of T-cell stimulation in vitro and in vivo and, unlike DEX, increased expression of the chemokines MCP-1 and MIP-1alpha. Both DEX and D(3) analog were associated with reduced expression of the NF-kappaB proteins c-Rel and Rel B but not Rel A. Combined DEX and D(3) analog treatment of DCs resulted in significant additive inhibition of pro-inflammatory cytokines, T-cell stimulation, chemokines, chemokine receptors, and NF-kappaB components. Additive inhibition was most striking for RANTES, CCR5, CCR7, and Rel B. The combined effects of the two hormonal pathways on DCs have unique immunomodulatory potential. 相似文献
3.
H L Henry S Fried G Y Shen S A Barrack W H Okamura 《The Journal of steroid biochemistry and molecular biology》1991,38(6):775-779
Three A-ring analogs of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)--2-nor-1,3-seco-1,25(OH)2D3 (2-nor analog), 2-oxa-3-deoxy-25-OH-D3 (2-oxa analog), and A-homo-3-deoxy-3,3-dimethyl-2,4-dioxa-25-OH-D3 (A-homo analog)--were tested for their ability to inhibit 25-OH-D3-1 alpha-hydroxylase (1 alpha-hydroxylase) in isolated mitochondria and to alter 25-OH-D3 metabolism in cultured chick kidney cells. The 2-nor and 2-oxa analogs were relatively potent (Kis of 60 and 30 nM, respectively, compared with 170 nM for 1,25(OH)2D3), whereas the A-homo analog was completely ineffective in inhibiting 1 alpha-hydroxylase activity. In contrast, all three analogs were able to repress 1 alpha-hydroxylase and induce 24-hydroxylase activity in cultured chick kidney cells, suggesting that this process is not one of direct action in the mitochondria, but is more likely to be a receptor-mediated one. 相似文献
4.
Locardi E Mattern RH Malaney TI Minasyan R Pierschbacher MD Taulane JP Goodman M 《Biopolymers》2002,66(5):326-338
We report the results of NMR studies and computer simulations of potent antagonists reflective of the alpha(IIb)beta(3) receptor-bound conformations. The peptides c[Mpa-(15)N-Arg(1)-(15)N-Gly(2)-(15)N-Asp(3)-(15)N-Phe(4)-(15)N-Arg(5)-Cys]-NH(2) (Phe-Arg analog) (Mpa: 3-mercaptopropionic acid) and c[Mpa-(15)N-Arg(1)-(15)N-Gly(2)-(15)N-Asp(3)-(15)N-Asp(4)-(15)N-Val(5)-Cys]-NH(2) (Asp-Val analog) were subjected to (15)N-edited NMR experiments to study the conformations of these peptides in the absence and in the presence of alpha(IIb)beta(3) receptor. The NMR studies of the Phe-Arg analog, a selective alpha(IIb)beta(3) antagonist, resulted in distinctly different experimental data in the presence and absence of the receptor. The computer simulations for this peptide resulted in one large family of structures consistent with the experimental data. This conformation suggests a type I beta-turn spanning residues Arg(1) and Gly(2) when bound to the receptor and we were able to establish a model for the three dimensional arrangement of the pharmacophores. The studies on the Asp-Val analog, an alpha(v)beta(3) antagonist that binds to the alpha(IIb)beta(3) with moderate affinity, resulted in conformations that are not as well defined as those for the Phe-Arg analog but are consistent with the model established for this analog. These results are important for the design of novel alpha(IIb)beta(3) antagonists. 相似文献
5.
R F Williams C L Mumford G A Williams L J Floyd M J Aivaliotis R A Martinez A K Robinson L D Barnes 《The Journal of biological chemistry》1985,260(25):13794-13802
A photoaffinity analog of colchicine, 6-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine, was synthesized by reacting deacetylcolchicine or [3H]deacetylcochicine with N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate. Homogeneity of the photoaffinity analog was established by thin-layer chromatography and high-pressure liquid chromatography. The structure of the photoaffinity analog was determined by 1H and 13C NMR, infrared and ultraviolet-visible spectroscopies, and elemental analysis. Binding of 6-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine to bovine renal tubulin was measured by competition with [3H]colchicine. The value of the apparent Ki for the photoaffinity analog was 0.28 microM in the concentration range of 0.8-1.2 microM of the analog. A value of 0.50 microM for the apparent Kd was measured by the direct binding of the tritiated photoaffinity analog to tubulin. The analog is slightly more potent an inhibitor of microtubule formation than colchicine. The photoaffinity analog reacted with renal tubulin upon irradiation with a mercury lamp equipped with a 420-nm cutoff filter. Spectral and radiochemical analyses of the tubulin after photolysis and dialysis have demonstrated a stoichiometric incorporation of the photoaffinity analog in the alpha-subunit of the tubulin. Covalent labeling of tubulin with the photoaffinity analog decreases the extent of [3H]colchicine binding by more than 90%. 相似文献
6.
Following up on the observation that the dynorphin analog [Pro(3)]Dyn A(1-11)-NH(2) 2 possesses high affinity and selectivity for the kappa opioid receptor, a number of related peptides were prepared and characterized by radioligand binding and [(35)S]GTPgammaS assays. While incorporation of 2-azetidine carboxylic acid in position 3 led to the equally potent analog 3, the corresponding analog containing piperidine-2-carboxylic acid showed a nearly 90-fold reduction in kappa affinity. Differential preferred bond angles phi in the three building blocks might account for these observations. Compounds 2 and 3 were kappa antagonists with IC(50) values of 380 and 350 nM, respectively. The Sar(3) analog 7 and the Sar(2) analog 8 were kappa agonists, with greater selectivity than Dyn A(1-11)-NH(2) 1. In view of their high kappa affinities (8: K(i) = 1.5 nM; 2: K(i) = 2.4 nM), the new analogs were surprisingly weak kappa agonists or antagonists, e.g., the EC(50) value for the agonist 8 was 280 nM. Different kappa receptor subtypes in binding vs functional assays can not account for these results, since both assays were performed using the same membrane preparation. 相似文献
7.
Comparison of the reactions of chemically reactive analogs of U-G-A and of A-U-G with ribosomes of Escherichia coli. 总被引:4,自引:3,他引:1
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The chemically reactive analog of U-G-A, 5'-(4-(Bromo-[2-14C] acetamido) phenylphospho) - uridylyl-(3'-5') - guanylyl-(3'-5') adenosine has a 20 fold lower affinity to 70S ribosomes than the corresponding analog of A-U-G though the U-G-A analog also preferentially reacts with protein S18 of 70S ribosomes. This reaction programs ribosomes for EF-T dependent Trp-tRNATrp-suIII binding. Therefore, it is concluded that this protein is part of the A'-site of the ribosomal codon binding site. Reaction of the U-G-A analog with 30S subunits lead to a predominant crosslinking of U-G-A to proteins S4 and S18. In contrast, a comparable reaction of the A-U-G analog with 30S subunits lead to a predominant crosslinking of A-U-G to proteins S4 and S12 (Pongs, O., Stoffler, G.A., Lanka, E., (1975) J. Mol. Biol. 99, 301). Since protein S12 is located at the 'P' site of the ribosomal codon binding site, it is proposed that the U-G-A analog does not bind at this site. 相似文献
8.
F Fahrenholz G Tóth P Crause P Eggena I L Schwartz 《The Journal of biological chemistry》1983,258(24):14861-14867
The photoreactive analog of vasopressin [1,6-alpha-aminosuberic acid, 3-(p-azidophenylalanine), 8-arginine] vasopressin [( Asu1,6, Phe (p-N3)3]AVP) has been synthesized. This analog retains a high binding affinity for the vasopressin receptor in plasma membranes from bovine kidney inner medulla (apparent dissociation constant, KD = 8.5 X 10(-9) M). [Asu1,6, Phe (p-N3)3] AVP was found to be biologically active in triggering the characteristic increase in toad bladder permeability to water. Photolysis of the analog in the presence of the toad bladder results in a hydroosmotic response which persists, in spite of repeated washings, for more than 18 h. The irreversible stimulation of the bladder is inhibited when photolysis is carried out in the presence of vasopressin. Our findings indicate that with photoactivation [Asu1,6, Phe(p-N3)3]AVP binds covalently to hormonal receptors and forms an active hormone-receptor complex. This analog, therefore, is a suitable tool for studies of hydroosmotic receptor function and for receptor isolation. 相似文献
9.
Nguyen HP Seto NO Cai Y Leinala EK Borisova SN Palcic MM Evans SV 《The Journal of biological chemistry》2003,278(49):49191-49195
Human ABO(H) blood group glycosyltransferases GTA and GTB catalyze the final monosaccharide addition in the biosynthesis of the human A and B blood group antigens. GTA and GTB utilize a common acceptor, the H antigen disaccharide alpha-l-Fucp-(1-->2)-beta-d-Galp-OR, but different donors, where GTA transfers GalNAc from UDP-GalNAc and GTB transfers Gal from UDP-Gal. GTA and GTB are two of the most homologous enzymes known to transfer different donors and differ in only 4 amino acid residues, but one in particular (Leu/Met-266) has been shown to dominate the selection between donor sugars. The structures of the A and B glycosyltransferases have been determined to high resolution in complex with two inhibitory acceptor analogs alpha-l-Fucp(1-->2)-beta-d-(3-deoxy)-Galp-OR and alpha-l-Fucp-(1-->2)-beta-d-(3-amino)-Galp-OR, in which the 3-hydroxyl moiety of the Gal ring has been replaced by hydrogen or an amino group, respectively. Remarkably, although the 3-deoxy inhibitor occupies the same conformation and position observed for the native H antigen in GTA and GTB, the 3-amino analog is recognized differently by the two enzymes. The 3-amino substitution introduces a novel intramolecular hydrogen bond between O2' on Fuc and N3' on Gal, which alters the minimum-energy conformation of the inhibitor. In the absence of UDP, the 3-amino analog can be accommodated by either GTA or GTB with the l-Fuc residue partially occupying the vacant UDP binding site. However, in the presence of UDP, the analog is forced to abandon the intramolecular hydrogen bond, and the l-Fuc residue is shifted to a less ordered conformation. Further, the residue Leu/Met-266 that was thought important only in distinguishing between donor substrates is observed to interact differently with the 3-amino acceptor analog in GTA and GTB. These observations explain why the 3-deoxy analog acts as a competitive inhibitor of the glycosyltransferase reaction, whereas the 3-amino analog displays complex modes of inhibition. 相似文献
10.
K R Latham J W Apriletti N L Eberhardt J D Baxter 《The Journal of biological chemistry》1981,256(23):12088-12093
Certain cellular responses to thyroid hormones appear to be mediated by non-histone chromatin protein receptors. Purification of these proteins is important for an investigation of the detailed mechanisms of their regulatory role. In the present studies, we report the development of an affinity chromatographic system that can be used to purify thyroid hormone receptors solubilized from nuclei. Amine-substituted hormone analogs were prepared with D and L isomers of T3; these bind to the receptor. This finding supports the hypothesis that thyroid hormones fit into the receptor with the amino groups accessible from outside the binding site. Although L-triiodothyronine (LT3) (the naturally occurring isomer) binds more tightly (relative Kd = 1.0 nM) to the nuclear receptor than D-triiodothyronine (DT3) (relative Kd = 2.0 nM), the amine-substituted analog of DT3 binds more tightly than the LT3 analog (DT3 analog, relative Kd = 40 nM; LT3 analog, relative Kd = 1500 nM). Agarose-based gels containing DT3 and LT3 covalently coupled by their amino groups were also prepared. Binding of receptor to these gels was biospecific in that it could be inhibited by prior incubation of the receptors with LT3. In addition, as predicted by the analog studies, the DT3 affinity gels were more effective than LT3 gels in adsorbing receptor. Elution of receptor from the LT3-derived gels was achieved in a predicted volume and concentration of counter-ligand in elution buffer. These results suggest that affinity chromatography can be applied to the purification of thyroid hormone receptors. 相似文献
11.
I Hillmar T Muramatsu N Z?llner 《Hoppe-Seyler's Zeitschrift für physiologische Chemie》1984,365(1):33-41
2-Acetyl-S-octadecyl-rac-1-thioglycero-3-phosphocholine, the thio analog of platelet-activating factor, in concentrations of 10(-6) M to 10(-12) M in the medium, lowers cAMP-concentrations in rat hepatocytes. In a concentration of 10(-4) M, the thio analog aggregates human platelets irreversibly, above 10(-5) M aggregation shows a reversible course. Compared with the saturated or unsaturated ether analogs, the thio compound shows less platelet-aggregating potency. We have correlated this difference in platelet aggregation with reduced cAMP-depressing activity of the thio analog (compared with saturated and unsaturated 2-acetyl-1-O-alkyl-sn-glycero-3-phosphocholines). 相似文献
12.
The syntheses of a novel uridine diphosphate galactose (UDP-Gal) analog, (UDP-2,4,6-tri-O-acetyl-3-S-acetyl-3-thio-alpha-D-galactopyranose) (11) and the thiolpyridine protected (Uridine 5'-[3-S-(2-S-pyridyl)-3-thio-alpha-D-galactopyranosyl diphosphate) analog (12) are described. The reported synthesis relies on the novel use of thiolpyridine to generate 12 which is a suitably protected intermediate for generating a UDP-thioGal derivative by reduction prior to enzyme transfer via beta-1,4-galactosyltransferase. 相似文献
13.
Hatcher MA Peleg S Dolan P Kensler TW Sarjeant A Posner GH 《Bioorganic & medicinal chemistry》2005,13(12):3964-3976
A series 5-8 of 1- and 3-CH(2)OH 19-nor analogs of the hormone calcitriol (1) has been prepared. Surprisingly, 19-nor 1alpha-CH(2)OH analog 5a is more antiproliferative at 100 nM concentration than the corresponding regioisomeric analog 6a with the natural 1alpha-OH group, and 1alpha-CH(2)OH hybrid analog 7a is similar in antiproliferative potency to calcitriol (1) even at low nanomolar concentrations. 相似文献
14.
E H Blaine 《Prostaglandins》1983,26(5):805-815
A recently discovered isosterically-modified prostaglandin analog, 4-(3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-2-thiazolidinyl ] propyl) benzoic acid, was studied in conscious Na-deficient dogs to determine if this compound could reverse the deleterious renal effects induced by inhibition of renal cyclooxygenase. Indomethacin (2 mg/kg i.v.) reduced renal function significantly in all dogs studied: GFR decreased from 38 +/- 3 to 26 +/- 1 ml/min (P less than 0.01) and ERPF from 124 +/- 15 to 79 +/- 8 ml/min (P less than 0.01). On separate occasions, the six dogs used in this study were treated with a saline placebo intravenously or with the PG analog (0.1 mg/kg i.v.) 60 min after receiving indomethacin. After placebo treatments renal function remained suppressed for the duration of observation (2 hours). After treatment with PG analog, GFR was restored to pre-indomethacin levels within 1 hour (36 +/- 3 ml/min) and remained at this level or higher for the duration of the experiment. ERPF was restored to pre-indomethacin levels within 30 min of PG analog injection (140 +/- 7 ml/min) and subsequently rose ml/min) for the duration of the experiment. Urinary electrolyte excretion was suppressed by indomethacin and despite the large increase in ERPF, Na excretion was not augmented by PG analog. This study demonstrates that a synthetic, isosterically-modified prostaglandin analog can effectively reverse the hemodynamic effects of non-steroidal antiinflammatory drug treatment on renal function while not affecting renal Na excretion. 相似文献
15.
Posner GH Jeon HB Sarjeant A Riccio ES Doppalapudi RS Kapetanovic IM Saha U Dolan P Kensler TW 《Steroids》2004,69(11-12):757-762
Based on an X-ray crystal structure determination, the A-ring stereochemistry of hybrid analog QW-1624F2-2 (1alpha-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitamin D3) is revised to be 1alpha-CH2OH-3beta-OH. This analog is shown to be approximately 80-100 times less calciuric than the natural hormone 1alpha,25-dihydoxyvitamin D3. This analog is shown also to be non-genotoxic in three different standard assays. 相似文献
16.
Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluation 总被引:1,自引:0,他引:1
Posner GH Suh BC Petersen KS Dolan P Agoston ES Kensler TW Koh JT Peleg S 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):213-221
17.
S V Nedel'kina I N Leonova R I Salganik T Iu Zenkova L M Va?ner 《Biokhimii?a (Moscow, Russia)》1985,50(8):1284-1289
It was shown that the alkylating analog of cytochrome P-450 substrate - 4-bromomethyl-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyl effectively inhibits in vitro the activities of monooxygenases, glutathione-S-transferases and esterases from the abdomen of the house fly Musca domestica L. The non-alkylating analog (RH) appeared to be a very weak inhibitor of these enzymes. It was demonstrated that the inhibitory action of the alkylating analog consists in its covalent binding to the enzyme protein. Topical application of the cytochrome P-450 alkylating analog on insects led to a decrease of the enzyme activity by approximately 20%. 相似文献
18.
Meurer LC Finke PE Mills SG Walsh TF Toupence RB Debenham JS Goulet MT Wang J Tong X Fong TM Lao J Schaeffer MT Chen J Shen CP Sloan Stribling D Shearman LP Strack AM Van der Ploeg LH 《Bioorganic & medicinal chemistry letters》2005,15(3):645-651
Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c, (hCB1 IC(50)=1.3 and 1.7 nM, respectively) as potent and selective hCB1 inverse agonists. Their synthesis and biological activities are described herein. 相似文献
19.
20.
The effect of low concentrations of a specifically designed sterol-24-transmethylase inhibitor, 25-aza-24, 25-dihydrozymosterol (10) on sterol production in Saccharomyces cerevisiae was examined. The synthesis of cholesta-5,7,22,24-tetraen-3beta-ol (4), its 7,22,24 analog (15) and the 7,24 analog (5) coupled with the availability of zymosterol (6) and cholesta-5,7,24-3beta-ol (3) derivatives facilitated a search for these sterols in cultures treated with this inhibitor. When S. cerevisiae was grown in the presence of 1.3 and 5 muM 10, it produced no ergosterol but accumulated zymosterol (6), cholesta-5,7,22,24-tetraen-3beta-ol (4) and related C27 sterols (3 and 5). These results indicate blockage of the side chain methylation that normally occurs during the biosynthesis of ergosterol in yeast by compound 10 is efficient. The cholesta-5,7,22,24-tetraen-3beta-ol is a close structural analog of provitamin D3 (7-dehydrocholesterol). The inhibited yeast thus provides a source of a potentially new provitamin D3 substitute. 相似文献