共查询到20条相似文献,搜索用时 31 毫秒
1.
Li-Juan Li Xin-Min Pan Xiutian Sima Zhao-Hui Li Lu-Shun Zhang Hong Sun Yi Zhu Wei-Bo Liang Lin-Bo Gao Lin Zhang 《Molecular biology reports》2012,39(12):11217-11223
Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction–restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR?=?2.09, 95?% CI: 1.29–3.38; C vs. A: OR?=?1.45, 95?% CI: 1.10–1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR?=?4.63, 95?% CI: 1.92–11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA. 相似文献
2.
Adrian Wai-Hing Cheung John Brinkman Fariborz Firooznia Alexander Flohr Joseph Grimsby Mary Lou Gubler Kevin Guertin Rachid Hamid Nicholas Marcopulos Roger D. Norcross Lida Qi Gwendolyn Ramsey Jenny Tan Yang Wen Ramakanth Sarabu 《Bioorganic & medicinal chemistry letters》2010,20(14):4140-4146
7-N-Acetamide-4-methoxy-2-aminobenzothiazole 4-fluorobenzamide (compound 1) was chosen as a drug-like and non-xanthine based starting point for the discovery of A2B receptor antagonists because of its slight selectivity against A1 and A2A receptors and modest A2B potency. SAR exploration of compound 1 described herein included modifications to the 7-N-acetamide group, substitution of the 4-methoxy group by halogens as well as replacement of the p-flouro-benzamide side chain. This work culminated in the identification of compound 37 with excellent A2B potency, modest selectivity versus A2A and A1 receptors, and good rodent PK properties. 相似文献
3.
Guo Yang Huitong Zhou Rachel H. Forrest Qian Fang Yuzhu Luo Jon G. H. Hickford 《Molecular biology reports》2013,40(8):4805-4810
The β3-adrenergic receptor (ADRB3) regulates thermogenesis and lipolysis in brown and white adipose tissue. Previously, sixteen ovine ADRB3 haplotypes have been defined. In this study, the relationship between these ADRB3 haplotypes and variation in post-weaning growth was investigated in 797 New Zealand Suffolk lambs from 38 sire lines and eight studs, using PCR-SSCP and General Linear Mixed-effects Models. Seven haplotypes were found in these sheep and they comprised five previously reported intron sequences and four previously reported 3′UT sequences. The frequencies of the various diplotypes ranged from 0.1 to 17.6 % and individual haplotypes from 0.8 to 32.5 %. The presence of haplotype A-b was associated with a decreased weaning-weight (P = 0.001). Sheep with the B-c/F-e diplotype had a higher mean weaning-weight than those with A-b/B-c or A-b/E-e (P < 0.05). The presence of C-a was found to be associated with increased post-weaning growth (P = 0.008), while the presence of B-c was associated with decreased post-weaning growth (P = 0.005). Sheep with A-b/C-a had higher mean post-weaning growth than those with A-b/A-b, A-b/B-c, B-c/B-c, B-c/E-e or B-c/F-e (P < 0.05). Sheep with B-c/B-c had lower mean post-weaning growth than those with A-b/C-a or B-c/C-a (P < 0.05). Additive effects for the different forms of the B-c haplotypes on post-weaning growth were identified. The effects of the ovine ADRB3 haplotypes on weaning-weight and post-weaning growth confirm that they could be used as a candidate gene-marker for improving sheep growth. 相似文献
4.
Definitions are proposed for the independent and joint contributions that the chemical groups A and B make to the free energy of association of the ligand A?B with a receptor. The definitions are independent of the choice of the standard state and are consistent with the basic thermodynamic cycle relating the association of the ligands A?B, A?Y and X?B to the receptor Rappaport 1976. The basic idea is the use of the excess free energy of association of the ligand A?Y over the free energy of association of the reference ligand X?Y as the measure of the “independent” contribution of the group A to the binding. This definition allows the free energy of association of the ligand A?B to be written as the sum of the independent contributions of the groups A and B, their joint contribution, and an invariant free energy of association of the reference ligand with any receptor. With the appropriate definition of the receptor-reference ligand complex, water can be chosen as the reference ligand. Using ΔG(A?OH)?AG(HOH), ΔG(H?B?H)?ΔG(HOH) and ΔG(HO?C)?ΔG(HOH) as the definitions of the “independent” contributions of the chemical groups A, B and C to the binding of the ligand A?B?C, the joint contribution of the groups A and C to the binding is ΔG(A?B?C) ? ΔG(A?B?H) ? ΔG(H-B-C) + ΔG(H?B?H). 相似文献
5.
George N. Phillips Florante A. Quiocho Ronald L. Sass Peter Werness Herschell Emery Furn F. Knapp G.J. Schroepfer 《Bioorganic chemistry》1976,5(1):1-10
Previous studies have established that hydride reduction of 3β-benzoyloxy-5α-cholest-8(14)-en-15-one yields two epimers (at C-15) of 5α-cholest-8(14)-en-3β,15-diol which were designated as diol A and B. Efficient enzymatic conversion of both compounds to cholesterol was observed. To determine the absolute configuration of the 15-OH function in the two compounds, the 3β-p-bromobenzoyl ester of diol B was prepared from 3β-p-bromobenzoyloxy-5α-cholest-8(14)-en-15-one by reduction with sodium borohydride. Crystals of the derivative were found to belong to the space group P1, with unit cell parameters; , , , α = 93.05°, β = 100.27°, γ = 90.82°, and one molecule per unit cell. Least-squares refinement of the structure was carried out to final R value of 0.14. The configuration of the hydroxyl group at the 15 position of diol B has been determined to be β. 相似文献
6.
V. A. Khripach V. N. Zhabinskii Yu. V. Ermolovich O. V. Gulyakevich A. R. Mekhtiev P. A. Karalkin 《Russian Journal of Bioorganic Chemistry》2012,38(4):438-446
A series of 241-norbrassinolide biosynthetic precursors containing 3??-OH, 3-keto, ??2- or 2??,3??-epoxy functional groups less polar than 2??,3??-diol group in A-ring, and (22R,23R)-diol group in the side chain, was synthesized. Their biological activity as the proliferation regulators in MCF-7 human breast cancer and LNCaP human prostate adenocarcinoma cells was studied. It was shown that the majority of the derivatives obtained effectively suppress cell proliferation. The dependence of proliferation on the concentration of the studied compounds was found in LNCaP human prostate adenocarcinoma cells (IC50 = 13?C28 ??M at 72 h of incubation in a medium containing 10% FBS, and suppression of DNA biosynthesis). Some compounds stimulated apoptosis (23?C33%), blocked the cell cycle in S- and G2/M-phases, and induced a partial detachment of cells during a prolonged incubation. 相似文献
7.
Ibicella lutea and Proboscidea louisiana, both of the Martyniaceae family, are known for rich glandular trichomes on their leaves and stems. Chemical investigations of the glandular trichome exudates on leaves of the two plants furnished three types of secondary metabolites, glycosylated fatty acids, glycerides (2-O-(3,6-diacetyloxyfattyacyl)glycerols and 2-O-(3-acetyloxyfattyacyl)glycerols) and dammarane triterpenes. The glycosylated fatty acids from I. lutea were determined to be 6(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-octadecanoic acid (1A), -eicosanoic acid (1B) and -docosanoic acid (1C), as well as their respective deacetyl congeners (2A, 2B and 2C), whereas P. louisiana furnished 8(S)-(6-O-acetyl-β-d-glucopyranosyloxy)-eicosanoic acid (3A) and -docosanoic acid (3B) and their respective deacetyl congeners (4A and 4B), together with 2B. Both plants contained 12 identical 2-O-[(3R,6S)-3,6-diacetyloxyfattyacyl]glycerols (5A-L), in which the fatty acyl moieties contained between 17 and 21 carbon atoms. The corresponding mono-acetyloxy compounds, 2-O-[(3R)-3-acetyloxyfattyacyl]glycerols (6A–L) were detected in both plants. Among these glycerides, ten compounds (5A, 5C, 5F, 5H, 5K, 6A, 6C, 6F, 6H and 6K) had iso-fattyacyl structures and four (5E, 5J, 6E and 6J) had anteiso-fattyacyl structures. A previously unknown dammarane triterpene, betulatriterpene C 3-acetate (7), was isolated together with three known dammarane triterpenes, 24-epi-polacandrin 1,3-diacetate (8), betulatriterpene C (9) and 24-epi-polacandrin 3-acetate (10) from I. lutea, whereas 12 dammarane triterpenes, named probosciderols A–L (12–23), and the known compound betulafolienetriol (11) were isolated from P. louisiana. The structures of these compounds were elucidated by spectroscopic analysis including 2D-NMR techniques and chemical transformations. The 6-O-acetylglucosyloxy-fatty acids 1A–C (42%) and the dammarane triterpenes 7–10 (31%) were the two most abundant constituents in the glandular trichome exudate of I. lutea, whereas the dammarane triterpenes 11–23 (47%) and the glucosyloxy-fatty acids (4A, 4B and 2B) (38%) were the most abundant constituents in the glandular trichome exudate of P. louisiana. 相似文献
8.
9.
Michele Michelin Simone C. Peixoto-Nogueira Tony M. Silva Jo?o A. Jorge Héctor F. Terenzi José A. Teixeira Maria de Lourdes T. M. Polizeli 《World journal of microbiology & biotechnology》2012,28(11):3179-3186
Aspergillus ochraceus, a thermotolerant fungus isolated in Brazil from decomposing materials, produced an extracellular ??-xylosidase that was purified using DEAE-cellulose ion exchange chromatography, Sephadex G-100 and Biogel P-60 gel filtration. ??-xylosidase is a glycoprotein (39?% carbohydrate content) and has a molecular mass of 137?kDa by SDS-PAGE, with optimal temperature and pH at 70?°C and 3.0?C5.5, respectively. ??-xylosidase was stable in acidic pH (3.0?C6.0) and 70?°C for 1?h. The enzyme was activated by 5?mM MnCl2 (28?%) and MgCl2 (20?%) salts. The ??-xylosidase produced by A. ochraceus preferentially hydrolyzed p-nitrophenyl-??-d-xylopyranoside, exhibiting apparent Km and Vmax values of 0.66?mM and 39?U (mg protein)?1 respectively, and to a lesser extent p-nitrophenyl-??-d-glucopyranoside. The enzyme was able to hydrolyze xylan from different sources, suggesting a novel ??-d-xylosidase that degrades xylan. HPLC analysis revealed xylans of different compositions which allowed explaining the differences in specificity observed by ??-xylosidase. TLC confirmed the capacity of the enzyme in hydrolyzing xylan and larger xylo-oligosaccharides, as xylopentaose. 相似文献
10.
Flavia Varano Daniela Catarzi Matteo Falsini Diego Dal Ben Michela Buccioni Gabriella Marucci Rosaria Volpini Vittoria Colotta 《Bioorganic & medicinal chemistry letters》2019,29(4):563-569
This paper describes the synthesis of novel 7-amino-thiazolo[5,4-d]pyrimidines bearing different substituents at positions 2, 5 and 7 of the thiazolopyrimidine scaffold. The synthesized compounds 2–27 were evaluated in radioligand binding (A1, A2A and A3) and adenylyl cyclase activity (A2B and A2A) assays, in order to evaluate their affinity and potency at human adenosine receptor subtypes. The current study allowed us to support that affinity and selectivity of 7-amino-thiazolo[5,4-d]pyrimidine derivatives towards the adenosine receptor subtypes can be modulated by the nature of the groups attached at positions 2, 5 and 7 of the bicyclic scaffold. To rationalize the hypothetical binding mode of the newly synthesized compounds, we also performed docking calculations in human A2A, A1 and A3 structures. 相似文献
11.
P. Mokarram M. Zamani S. Kavousipour F. Naghibalhossaini C. Irajie M. Moradi Sarabi S. V. Hosseini 《Molecular biology reports》2013,40(5):3851-3857
Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal cancer incidence differs widely among different geographic regions. In addition to mutational changes, epigenetic mechanisms also play important roles in the pathogenesis of CRCs. O6-methylguanine-DNA methyltransferase (O 6 -MGMT) is a DNA repair protein and in the absence of MGMT activity, G-to-A transition may accumulate in the specific genes such as K-ras and p53. To identify which CpG sites are critical for its downregulation, we analyzed the methylation status of the MGMT gene promoter in two sites in CRC patients. Then we compared the frequency of their methylation changes with the results of our previously reported K-ras gene mutation, APC2 and p16 methylation. MGMT methylation was examined in 92 tumor samples. A methylation specific PCR (MSP) method was performed for two loci of MGMT gene which described as MGMT-A and MGMT-B. The prevalence of MGMT-A, and MGMT-B methylation was 49/91 (53.8 %), and 83/92 (90.2 %), respectively. We detected high frequency of MGMT-B but not MGMT-A methylation in tumor tissues with APC2 methylation. Our results showed that MGMT-B methylation is significantly associated with K-ras gene mutation rather than MGMT-A (p = 0.04). Simultaneously, an inverse correlation was found between p16 and MGMT-B methylation simultaneously (p = 0.02). Our study indicated that hypermethylation of the specific locus near the MGMT start codon is critical for cancer progression. MGMT-B assessment that is associated with K-ras mutation can have a prognostic value in patients with CRC. 相似文献
12.
The isolation of oligosaccharides from the cell-wall polysaccharide of Lactobacillus casei, serological group C 总被引:3,自引:3,他引:0
1. A number of disaccharides and oligosaccharides have been isolated from the products of mild acid hydrolysis of the specific substance from Lactobacillus casei, serological group C. 2. The major disaccharide is O-β-d-glucopyranosyl-(1→3)-N-acetyl- d-galactosamine (B4) and evidence is presented for the structure of a tetrasaccharide composed of O-β-d-glucopyranosyl-(1→6)-d-galactose (B1) joined through its reducing end group to B4. 3. Disaccharide B1 is also a component of a trisaccharide O-β-d-glucopyranosyl-(1→6)-O-β- d-galactopyranosyl-(1→6)-N-acetyl-d-glucosamine (A7). 4. A number of other oligosaccharides have been shown to be related structurally. 5. The ability of certain of the oligosaccharides to inhibit the precipitin reaction has been studied. The disaccharide B1 is more effective as an inhibitor than gentiobiose and the trisaccharide A7 is considerably more effective than B1. 6. These results have been compared with those obtained previously for the composition of the cell wall. 相似文献
13.
Harbinder Singh Jatinder Vir Singh Manish K. Gupta Palwinder Singh Sahil Sharma Kunal Nepali Preet Mohinder S. Bedi 《Bioorganic & medicinal chemistry letters》2017,27(4):850-854
A library of forty 7,8-benzoflavone derivatives was synthesized and evaluated for their inhibitory potential against cholesterol esterase (CEase). Among all the synthesized compounds seven benzoflavone derivatives (A-7, A-8, A-10, A-11, A-12, A-13, A-15) exhibited significant inhibition against CEase in in vitro enzymatic assay. Compound A-12 showed the most promising activity with IC50 value of 0.78 nM against cholesterol esterase. Enzyme kinetic studies carried out for A-12, revealed its mixed-type inhibition approach. Molecular protein–ligand docking studies were also performed to figure out the key binding interactions of A-12 with the amino acid residues of the enzyme’s active site. The A-12 fits well at the catalytic site and is stabilized by hydrophobic interactions. It completely blocks the catalytic assembly of CEase and prevents it to participate in ester hydrolysis mechanism. The favorable binding conformation of A-12 suggests its prevailing role as CEase inhibitor. 相似文献
14.
K. Eisler B. Kamber B. Riniker W. Rittel P. Sieber M. de Gasparo F. Märki 《Bioorganic chemistry》1979,8(4):443-450
Five analogs of human insulin with d-Cys in different positions (A6, A7, A11, A6+11, B7) have been synthesized by the fragment condensation approach, combined with selective disulfide formation. All of them have physicochemical properties noticeably different from those of human insulin. They possess very low biological activity (0.03?1.2%, glucose oxidation in rat fat cells). In contrast, the potency for antibody binding ranges from 7 to 70% of that of insulin. The two analogs with d-Cys in positions A6 and A7 have been obtained in crystalline form. 相似文献
15.
Stephanie Federico Sara Redenti Mattia Sturlese Antonella Ciancetta Sonja Kachler Karl-Norbert Klotz Barbara Cacciari Stefano Moro Giampiero Spalluto 《PloS one》2015,10(12)
A new series of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) derivatives has been developed in order to explore their affinity and selectivity profile at the four adenosine receptor subtypes. In particular, the PTP scaffold was conjugated at the C2 position with the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole, a group believed to confer potency and selectivity toward the human (h) A2B adenosine receptor (AR) to the xanthine ligand 8-(1-(3-(trifluoromethyl)benzyl)-1H-pyrazol-4-yl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (CVT 6975). Interestingly, the synthesized compounds turned out to be inactive at the hA2B AR but they displayed affinity at the hA3 AR in the nanomolar range. The best compound of the series (6) shows both high affinity (hA3 AR Ki = 11 nM) and selectivity (A1/A3 and A2A/A3 > 9090; A2B/A3 > 909) at the hA3 AR. To better rationalize these results, a molecular docking study on the four AR subtypes was performed for all the synthesized compounds. In addition, CTV 6975 and two close analogues have been subjected to the same molecular docking protocol to investigate the role of the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole on the binding at the four ARs. 相似文献
16.
Three major peroxidases, designated as A, B2 and B2 from Solanum melongena leaves have been reported. Peroxidases-A, -B2 and -B2 were considered to be true peroxidases on the basis of k1:k4 ratio. The pH optima for the three enzymes were found to be 7·0, 6·0 and 6.0 respectively. These peroxidases differ in their k1:k4 ratio, in the effect of pH on this ratio and in the uric acid/guaiacol and o-dianisidine/guaiacol activity ratio. 相似文献
17.
Firooznia F Cheung AW Brinkman J Grimsby J Gubler ML Hamid R Marcopulos N Ramsey G Tan J Wen Y Sarabu R 《Bioorganic & medicinal chemistry letters》2011,21(7):1933-1936
The highly potent but modestly selective N-(2-amino-4-methoxy-benzothiazol-7-yl)-N-ethyl-acetamide derivative 2 was selected as the starting point for the design of novel selective A2B antagonists, due to its excellent potency, and good drug-like properties. A series of compounds containing nonaromatic amides or ureas of five- or six-membered rings, and also bearing an m-trifluoromethyl-phenyl group (shown to impart superior potency) was prepared and evaluated for their selectivity against the A2A and A1 receptors. This work resulted in the identification of compound 30, with excellent potency and high selectivity against both A2A and A1 receptors. 相似文献
18.
Faramarz Sohrabi Chah Hassan Mahmood Solouki Barat Ali Fakheri Nafiseh Mahdi Nezhad Bahram Masoudi 《Physiology and Molecular Biology of Plants》2018,24(6):1231-1243
In order to detect genomic regions with different effects for some of the physiological and biochemical traits of wheat, four experiments were conducted at Research Farm of Agricultural and Natural Resources Research Center of Zabol in 2015–2016 and 2016–2017 growing seasons. The experiments were carried out using four alpha lattice designs with two replications under non-stress and terminal heat stress conditions. Plant materials used in this study included 167 recombinant inbred lines and their parents (‘SeriM82’ and ‘Babax’). Six traits including grain yield (GY), proline content (PRO), water soluble carbohydrates (WSC), maximum efficiency of photosystem II (Fv/Fm), cytoplasmic membrane stability (CMS) and chlorophyll content (CHL) were evaluated. Genetic linkage map consisted of 211 AFLP marker, 120 SSR marker and 144 DArT markers with 1864 cm length and 4.4 cm mean distance. QTL analysis was carried out using a mixed-model-based composite interval mapping (MCIM) method. By the combined analysis of normal phenotypic values, 27 additive QTLs and five pairs of epistatic effects were identified for studied traits, among which two additive and one epistatic QTL showed significant QTL?×?environment interactions. By the combined analysis of stress phenotypic values, a total of 26 QTLs with additive effects and 5 epistatic QTLs were detected, among which one additive and one epistatic QTL showed QTL?×?environment interactions. Six QTLs with major effects (QGY-2B, QGY-2D, QPro-5B, QWSC-4A, QFv/Fm-6A and QCMS-4B), which were common between two conditions could be useful for marker-assisted selection (MAS) in order to develop heat tolerant and high-performance wheat varieties. 相似文献
19.
Dyslipidemia is a strong risk factor for cardiovascular disease among patients with type 2 diabetes (T2D). The aim of this study was to identify lipid-related genetic variants in T2D patients of Han Chinese ancestry. Among 4,908 Chinese T2D patients who were not taking lipid-lowering medications, single nucleotide polymorphisms (SNPs) in seven genes previously found to be associated with lipid traits in genome-wide association studies conducted in populations of European ancestry (ABCA1, GCKR, BAZ1B, TOMM40, DOCK7, HNF1A, and HNF4A) were genotyped. After adjusting for multiple covariates, SNPs in ABCA1, GCKR, BAZ1B, TOMM40, and HNF1A were identified as significantly associated with triglyceride levels in T2D patients (P < 0.05). The associations between the SNPs in ABCA1 (rs3890182), GCKR (rs780094), and BAZ1B (rs2240466) remained significant even after correction for multiple testing (P = 8.85×10−3, 7.88×10−7, and 2.03×10−6, respectively). BAZ1B (rs2240466) also was associated with the total cholesterol level (P = 4.75×10−2). In addition, SNP rs157580 in TOMM40 was associated with the low-density lipoprotein cholesterol level (P = 6.94×10−3). Our findings confirm that lipid-related genetic loci are associated with lipid profiles in Chinese patients with type 2 diabetes. 相似文献
20.
G. E. Milanovsky V. V. Ptushenko D. A. Cherepanov A. Yu. Semenov 《Biochemistry. Biokhimii?a》2014,79(3):221-226
The mechanisms of the ultrafast charge separation in reaction centers of photosystem I (PS I) complexes are discussed. A kinetic model of the primary reactions in PS I complexes is presented. The model takes into account previously calculated values of redox potentials of cofactors, reorganization energies of the primary P700+A 0 - and secondary P700+A 1 - ion-radical pairs formation, and the possibility of electron transfer via both symmetric branches A and B of redox-cofactors. The model assumes that the primary electron acceptor A0 in PS I is represented by a dimer of chlorophyll molecules Chl2A/Chl3A and Chl2B/Chl3B in branches A and B of the cofactors. The characteristic times of formation of P700+A 0 - and P700+A 1 - calculated on the basis of the model are close to the experimental values obtained by pump-probe femtosecond absorption spectroscopy. It is demonstrated that a small difference in the values of redox potentials between the primary electron acceptors A0A and A0B in branches A and B leads to asymmetry of the electron transfer in a ratio of 70: 30 in favor of branch A. The secondary charge separation is thermodynamically irreversible in the submicrosecond range and is accompanied by additional increase in asymmetry between the branches of cofactors of PS I. 相似文献