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1.
Nucleoside transporter inhibitors have potential therapeutic applications as anticancer, antiviral, cardioprotective, and neuroprotective agents. S6-(4-nitrobenzyl)mercaptopurine riboside (NBMPR) is a prototype inhibitor of the human equilibrative nucleoside transporter (hENT1), and is a high affinity ligand with a Kd of 0.1–1.0 nM. We have synthesized and flow cytometrically evaluated the binding affinity of a series of novel C2-purine position substituted analogs of NBMPR at the hENT1. The aim of this research was to understand the substituent requirements at the C2-purine position of NBMPR. Structure–activity relationships (SAR) indicate that increasing the steric bulk at the C2-purine position of NBMPR led to a decrease in binding affinity of these ligands at the hENT1. New high affinity inhibitors were identified, with the best compound, 2-fluoro-4-nitrobenzyl mercaptopurine riboside (7), exhibiting a Ki of 2.1 nM. This information, when coupled with the information obtained from other structure–activity relationship studies should prove useful in efforts aimed at modeling the NMBPR and analogs pharmacophore of hENT1 inhibitors.  相似文献   

2.
以黄河口生态恢复前后未恢复区(R0)、2007年恢复区(R2007)和2002年恢复区(R2002)的芦苇湿地为研究对象,研究了不同形态氮输入对湿地土壤N2O产生过程的影响与贡献.结果表明: 硝态氮(NO3--N)输入对恢复区湿地土壤N2O总产生量的影响远远大于铵态氮(NH4+-N),但两者均抑制了R0土壤的N2O总产生量.尽管NO3--N输入对R2002表层土壤N2O总产生量的影响明显大于R2007,但二者的N2O产生量均随氮输入量的增加而增加.恢复区湿地土壤的反硝化作用和硝化细菌反硝化作用受NO3--N输入的影响明显,而R0土壤产生N2O的生物过程受其影响并不显著.尽管NH4+-N输入对湿地土壤N2O的总产生量影响不大,但其输入整体促进了R0 土壤的硝化细菌反硝化作用、R2007土壤的硝化作用和R2002土壤的非生物作用.比较而言,NO3--N输入对R0、R2007和R2002湿地土壤N2O产生的非生物作用主要表现为抑制,NH4+-N输入则整体提高了R0和R2002湿地土壤非生物作用的N2O产生量,这与不同形态氮输入对土壤pH的调节作用密切相关.研究发现,NO3--N输入大大增加了湿地土壤的N2O总产生量,改变了原有湿地土壤生物作用和非生物作用的贡献模式,故生态恢复工程导致的营养盐输入(NO3--N)应受到特别关注.  相似文献   

3.
孙志高  孙文广 《生态学杂志》2016,27(4):1135-1144
以黄河口生态恢复前后未恢复区(R0)、2007年恢复区(R2007)和2002年恢复区(R2002)的芦苇湿地为研究对象,研究了不同形态氮输入对湿地土壤N2O产生过程的影响与贡献.结果表明: 硝态氮(NO3--N)输入对恢复区湿地土壤N2O总产生量的影响远远大于铵态氮(NH4+-N),但两者均抑制了R0土壤的N2O总产生量.尽管NO3--N输入对R2002表层土壤N2O总产生量的影响明显大于R2007,但二者的N2O产生量均随氮输入量的增加而增加.恢复区湿地土壤的反硝化作用和硝化细菌反硝化作用受NO3--N输入的影响明显,而R0土壤产生N2O的生物过程受其影响并不显著.尽管NH4+-N输入对湿地土壤N2O的总产生量影响不大,但其输入整体促进了R0 土壤的硝化细菌反硝化作用、R2007土壤的硝化作用和R2002土壤的非生物作用.比较而言,NO3--N输入对R0、R2007和R2002湿地土壤N2O产生的非生物作用主要表现为抑制,NH4+-N输入则整体提高了R0和R2002湿地土壤非生物作用的N2O产生量,这与不同形态氮输入对土壤pH的调节作用密切相关.研究发现,NO3--N输入大大增加了湿地土壤的N2O总产生量,改变了原有湿地土壤生物作用和非生物作用的贡献模式,故生态恢复工程导致的营养盐输入(NO3--N)应受到特别关注.  相似文献   

4.
玉米/花生间作行比和施磷对玉米光合特性的影响   总被引:1,自引:0,他引:1  
试验于2014—2015年设玉米/花生间作2∶2(R1)、2∶4(R2)和2∶8(R3)三种间作模式,研究了间作行比和施磷对玉米冠层光照日变化、功能叶的SPAD值、光合-光强响应曲线和光合-CO2响应曲线的影响,以探究间作玉米适应强光的光合机理.结果表明: 间作玉米冠层日均光照表现为R3>R2>R1;大口期至灌浆期,间作玉米穗位叶的SPAD值、表观量子效率(AQY)、光补偿点(LCP)、光饱和点(LSP)、光饱和时的最大净光合速率(LSPn)、羧化效率(CE)、最大电子传递速率(Jmax)、磷酸丙糖利用率(TPU)、气孔导度(gs)、蒸腾速率(Tr)和净光合速率(Pn)均表现为R3>R2>R1,胞间CO2浓度(Ci) 则为R1>R2>R3;蜡熟期R3间作玉米的AQY、LSPngs、CE、Jmax和TPU均低于R2间作玉米;施磷能提高AQY、LSPn、CE、Vc maxJmax和TPU等光合参数.这说明间作玉米gs、AQY、CE、Vc maxJmax和TPU随着光强增加逐渐提高是其增强利用强光能力的关键,但超过一定光强易早衰,施磷肥有助于增强玉米对强光的利用和延缓叶片衰老.  相似文献   

5.
为明确行距和播种量对冬小麦冠层光合有效辐射(PAR)垂直分布、生物量和籽粒产量的影响,在不增加水肥等投入的基础上,设置等行距(R1,20 cm+20 cm)、宽窄行(R2,12 cm+12 cm+12 cm+24 cm)两种行距方式和低(D1,120 kg·hm-2)、中(D2,157.5 kg·hm-2)、高(D3,195 kg·hm-2)3个播种量水平,分析不同处理组合下冬小麦主要生育时期冠层PAR的截获率及利用率、群体光合能力、生物量和产量差异。结果表明: 冬小麦冠层总PAR截获率、上层PAR截获率均表现为R1行距显著大于R2,而中层和下层PAR截获率则表现为R2大于R1,且在中层差异显著;从小麦开花至成熟期,相同播种量下R2行距光合势(LAD)、群体光合速率(CAP)、PAR转化率和利用率都显著高于R1,并以R2D2处理最大;冬小麦的群体生物量(BA)和不同层次叶片生物量(BL)均表现为随播种量增加而增加,但单株生物量(BP)则相反。在同一播种量下,BA、BL和BP均在开花期之后表现为R2行距高于R1,其中,BA、BP在成熟期行距间差异显著,中层和下层BL在D2、D3播种量下行距间差异显著;不同处理组合间冬小麦的穗数、穗粒数、千粒重、籽粒产量分别以R2D3、R2D1、R2D1、R2D2最大,其中,R2行距下千粒重、穗粒数和籽粒产量显著大于R1。综上,改变行距可以改善小麦冠层中下层PAR的截获量,增强冬小麦单株和群体光合能力、光合有效辐射的利用及转化效率,提高生物量和籽粒产量。在冬小麦高产栽培中,应重视通过优化田间结构,塑造麦田理想的群体光合结构,以充分利用单位土地面积上光照资源,挖掘作物自身的光合生产潜力,达到高产高效的目的。在本试验条件下,以R2D2配置群体光合能力、光合有效辐射利用率和产量最佳。  相似文献   

6.
Pyridoacridine ascididemin analogues have been reported as anticancer agents for their interesting antitumor activity against human cancer cells. A quantitative structure–activity relationship (QSAR) analysis of ascididemin analogues was attempted using the physicochemical parameters and the electrotopological state atom (ETSA) indices. This study indicates that the electron withdrawing substituents with higher MR (molar refractivity) value at R1 position favor the anti-tumor activity and the presence of NHR (R is hydrogen or alkyl group) at the R3 position has contribution to the anti-tumor activity. ETSA indices have been incorporated as independent variable in the QSAR model with physicochemical parameters. It clearly suggests the importance of atoms 2, 3, 4, 5, 6 and 7 to the anti-tumor activity.  相似文献   

7.
研究探索自组装短肽R2I4R2在人皮肤成纤维细胞体外三维培养的应用效果与对创伤修复过程的作用。通过圆二色谱仪分析不同时间、温度和离子条件对其二级结构的影响;刚果红染色宏观检测短肽自组装情况;体外培养人皮肤成纤维细胞探索细胞在R2I4R2形成的纳米纤维网络中的生长状态及凋亡情况;建立SD大鼠皮肤创伤模型,HE染色与免疫组织化学检测其对皮肤创伤修复的病理变化。结果表明,R2I4R2在不同条件下均可形成较为稳定的二级结构;自组装24h后可形成均一稳定的膜片状结构,为细胞三维培养提供支架;人皮肤成纤维细胞可在R2I4R2形成的纳米纤维网络三维环境中生长且状态良好;动物实验表明,短肽R2I4R2可减少炎症、促进新生血管生成、加速皮肤创伤修复过程。自组装短肽R2I4R2作为新的纳米支架材料,可用于细胞三维培养与皮肤创伤修复。  相似文献   

8.
Two novel five-coordinate cis-dioxorhenium(V) complexes of the general formula ReO2[R2NCH2CH2S][PPh3] (R2N=Et2N, complex 1 and R2N=(o-CH3O---C6H4N(CH2CH2)2N, complex 2) have been synthesized by reacting ReOCl3(PPh3)2 with the respective bidentate ligands R2NCH2CH2SH. The complexes have been characterized by elemental analysis, IR, NMR spectroscopies and X-ray crystallography. X-ray crystallographic studies showed that the coordination geometry around rhenium is distorted trigonal bipyramidal. The basal plane is defined by the two doubly bonded oxygen atoms and the sulfur of the bidentate ligand, while the nitrogen of the ligand and the phosphorus occupy the apical positions.  相似文献   

9.
[3H]Lysergic acid diethylamide (LSD) in the presence of 40 nM ketanserin labeled the 5-HT1A receptor subtype in rat hippocampal membranes. In the presence of guanosine triphosphate (GTP), the Bmax and affinity of [3H]LSD binding to the 5-HT1A binding site were significantly decreased. [3H]LSD in the presence of 40 nM WB4101 labeled the 5-HT2 receptor subtype in homogenates of rat frontal cortex. In contrast to the effect on [3H]LSD binding to the 5-HT1A binding site, GTP produced no significant effect on either the Bmax or the KD of [3H]LSD binding to the 5-HT2 binding site. Competition of 5-HT for [3H]LSD binding to the 5-HT2 binding site was best described by a computer-derived model assuming two binding sites. In the presence of GTP, the 5-HT competition curve was shifted significantly to the right with an approx. 3-fold increase in the IC50. These binding characteristics are consistent with [3H]LSD acting as an antagonist at the 5-HT2 receptor which has multiple affinity states for agonists and is coupled to a guanine nucleotide regulatory subunit. Thus, [3H]LSD has binding characteristics consistent with it acting as an agonist at the 5-HT1A receptor subtype but as an antagonist at the 5-HT2 receptor subtype in rat brain.  相似文献   

10.
The noncompetitive blocker (NCB) site of the γ-aminobutyric acid (GABA)-gated chloride channel is the target for many important insecticides and potent convulsants. This site is specifically blocked by 3H ethynylbicycloorthobenzoate (3H EBOB) and other trioxabicyclooctane radioligands and might be suitable for affinity probes with an appropriate heterocyclic substituent and linker moiety. Optimal potency at the NCB site is achieved with 5e-tert-butyl-2e-[4-(substituted-ethynyl)phenyl]-1,3-dithianes compared with analogs in which the butyldithiane portion is replaced with butyldithiane-sulfoxide or -sulfone, n-propyltrioxabicyclooctane or dioxatricyclododecene. Three positions were examined for coupling the linker and dithiane: C-2 of the dithiane; a branched substituent within the alkynyl moiety; the terminus of a straight chain extension from the ethynyl group, which proved to be the best. Optimized linkers for addition to the ethynylphenyldithiane to achieve appropriate length and fit within the active site, i.e. receptor potency, are CH2OCH2C(O)SCH2CH2(SH or NH2) and the corresponding thiolates and amides. Several compounds with these spacers block the chloride channel, measured as inhibition of 3H EBOB binding, at 4–50 nM.  相似文献   

11.
估测水稻叶层氮浓度的新型蓝光氮指数   总被引:3,自引:0,他引:3  
基于不同氮素水平与品种类型的多个田间试验,综合分析了水稻冠层高光谱植被指数与叶层氮浓度的定量关系.结果表明:对氮反应最敏感的波段为红光665~675 nm、蓝光490~500 nm和红边区域波段680~760 nm.400~2500 nm波段范围内两波段植被指数与水稻叶层氮浓度相关性最好的是550~600 nm与500~550 nm,属绿光波段组合,决定系数(R2)最高的是比值指数SR(533,565).以3个蓝光波段构建的光谱参数R434/(R496+R401)(蓝光氮指数)与水稻叶层氮浓度呈极显著的直线相关关系,与SR(533,565)相比,该参数显著提高了对叶层氮浓度的预测性.独立资料检验结果显示,R434/(R496+R401)对水稻叶层氮浓度具有较好的预测性,检验根均方差(RMSE)和相对误差(RE)值分别为9.67%和8%,是一种适合于水稻叶层氮浓度估测的良好高光谱植被指数.  相似文献   

12.
A series of 2-(2,3-dimethoxyphenyl)-4-(aminomethyl)imidazole derivatives was prepared and their affinity for dopamine D2 and D3 receptors was measured using in vitro binding assays. Several oxadiazole analogues were also prepared and tested for their affinity for dopamine D2 and D3 receptors. The results of receptor binding studies indicated that the incorporation of an imidazole moiety between the phenyl ring and the basic nitrogen did not significantly increase the selectivity for dopamine D3 receptors, whereas the incorporation of an oxadiazole at the same region resulted in a total loss of affinity for both dopamine receptor subtype binding sites. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinomethyl)imidazole (5i), which has a D3 receptor affinity of 21 nM and a 7-fold selectivity for D3 versus D2 receptors. The binding affinity for σ1 and σ2 receptors was also measured, and the results showed that several analogues were selective σ1 receptor ligands.  相似文献   

13.
The affinity of purified human vitamin D-binding protein from serum (DBP) for 25-hydroxyvitamin D3 (25-OHD3) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was measured in the presence of free fatty acids (FFA), cholesterol, prostaglandins and several drugs. Mono- and polyunsaturated fatty acids markedly decreased the affinity of both 25-OHD3 and 1,25-(OH)2D3 for DBP, whereas saturated fatty acids (stearic and arachidic acid), cholesterol, cholesterol esters, retinol, retinoic acid and prostaglandins (A1 and E1) did not affect the apparent affinity. Several chemicals known to decrease the binding of thyroxine to its plasma-binding protein did not affect the affinity of DBP.

The apparent affinity of DBP for both 25-OHD3 and 1,25-(OH)2D3 decreased 2.4- to 4.6-fold in the presence of 36 μM of linoleic or arachidonic acid, respectively. Only a molar ratio of FFA:DBP higher than 10,000 was able to decrease the binding of 25-OHD3 to DBP by 20%. Much smaller ratio's of FFA:DBP (25 for arachidonic and 45 for oleic acid), however, decreased the binding of 1,25-(OH)2D3 to DBP. These latter ratio's are well within the physiological range. The addition of human albumin in a physiological albumin:DBP molar ratio did not impair the inhibitory effect of linoleic acid on the binding of [3H]25-OHD3 to DBP. The binding and bioavailability of vitamin D metabolites thus might be altered by mono- and polyunsaturated but not by saturated fatty acids.  相似文献   


14.
A new method has been developed for the preparation of nitroaryl transition metal complexes using copper(II) nitrate in the presence of acetic anhydride (Menke conditions) to directly nitrate an aryl group which is already σ-bound to a transition metal centre. Under these conditions ruthenium(II) aryl complexes of the type: (where R1=R2=H; R1=H, R2=CH3; R1=CH3, R2=H) react to yield three distinct types of nitroaryl-containing products (I–III).

The preparation and characterisation of these compounds are described. X-ray crystallographic data for one example of each of the three types of compound, are also reported. The compounds that have been studied crystallographically are Ru(C6H4NO2-4)(η2-O2CCH3)(CO)(PPh3)2 (1a), C45H37NO5P2Ru·(CH2Cl2)0.5, a = 20.254(5), b=19.437(8), c=22.629(3) Å, β=115.390(10)°, monoclinic, space group C2/c, Z=8; Ru(C6H4N[O]O-2)- Cl(CO)(PPh3)2 (4a), C43H34ClNO3P2Ru, a=9.331(3), b=12.443(2), c=16.346(3) Å, =82.81(2), β=85.03(2), γ=74.76(2)°, triclinic, space group P , Z=2; Ru(C6H2CH3-2,NO2-4,N[O]O-6)Cl(CO)(PPh3)2 (5b), C44H35Cl- N2O5P2Ru·(CH2Cl2)2, a=19.497(3), b=14.502(3), c=19.340(5) Å, β=122.79(1)°, monoclinic, space group Cc, Z=4.  相似文献   


15.
16.
Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3–14 nM while agonists—apomorphine and dopamine gave IC50 values of 2.5 and 10 μM, respectively suggesting a D2 type receptor.

Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 μM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 × 108 M−1 min−1 and 5.0 × 10−2 min−1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM.

During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38–60 fmol/mg protein or 570–1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years Significantly, at lower foetal ages (16–24 weeks) the [3H]spiperone binding sites exhibited a heterogeneity with a high (KD, 13–85 pM) and a low (KD, 1.2–4.6 nM) affinity component, the former accounting for 13–24% of the total binding sites. This heterogeneity persisted even when sulpiride was used as a displacer. The number of high affinity sites increased from 16 weeks to 24 weeks and after 28 weeks of gestation, all the binding sites showed only a single high affinity.

GTP decreased the agonist affinity as observed by dopamine competition of [3H]spiperone binding in 20-week-old foetal striata and at all subsequent ages. GTP increased IC50 values of dopamine 2 to 4.5 fold and Hill coefficients were also increased becoming closer to one suggesting that the dopamine receptor was susceptible to regulation from foetal life onwards.  相似文献   


17.
In this study we evaluate the uptake by murine dendritic cells (DCs) of different synthetic, branched cationic peptide structures with a view to facilitating peptide epitope delivery. The level of cell uptake by fluorescenated peptides was measured by flow cytometry following quenching of extracellular fluorescence with trypan blue. Branched peptides containing either N-terminal arginine or N-terminal lysine residues were able to mediate cell entry but the peptide containing four arginine residues in a branching configuration (R4) was found to be superior not only to other branched peptides in translocating to the cell interior and also to a peptide containing four arginine residues arranged linearly. Fluorescenated R4 was found to be localized within intracellular vesicle-like compartments as well as being distributed throughout the cell cytoplasm. Uptake of R4 utilized an energy-dependent process that appeared to involve phosphatidylinositol-3-kinase and could induce intermediate levels of DC maturation. R4 when conjugated to a T-helper cell and CTL epitope construct was able to induce antigen-specific CD8+ T-cell mediated immune responses in mice when administered in adjuvant as were DCs that were pulsed with this construct and then matured with LPS. Fluorescenated R4 was also found to translocate into the interior of other cell types indicating that it may be useful for the delivery of peptide cargo into other specialized cells.  相似文献   

18.
High affinity, specific [3H]5-hydroxytryptamine (5-HT) binding to spinal cord synaptosomes was examined to identify the 5-HT receptor subtypes present. Computer nonlinear regression analysis of competition studies employing 8-OH-DPAT indicated that this 5-HT1A selective agonist demonstrated high affinity competition (Ki = 1.3 nM) for 24.6 ± 0.7% of the total [3H]5-HT binding sites. Competition studies employing the 5-HT1B selective agonist RU24969, in the presence of 100 nM 8-OH-DPAT, indicated that RU24969 demonstrated high affinity (Ki = 1.1 nM) competitive inhibition for 26.2 ± 1.4% of all [3H]5-HT binding sites. Neither 5-HT1C, 5-HT1D, 5-HT2 nor 5-HT3 selective compounds demonstrated any high affinity competition for the residual 49% of specific [3H]5-HT binding. Therefore, three major classes of [3H]5-HT binding sites could be demonstrated in spinal cord synaptosomes: 5-HT1A, 5-HT1B and a novel [3H]5-HT binding site which respectively represented 25, 26 and 49% of spinal cord synaptosomal [3H]5-HT binding. Further studies focusing on the function of the latter binding site are needed to determine if the presently identified novel binding site is the major 5-HT1 receptor subtype present in spinal cord.  相似文献   

19.
Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG) E1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE1 was inhibited in a dose dependent fashion by PGE2>PGE1>PGA1>PGF2=PGA1>PGB1=PGB2≥PGD2. PGE1 metabolites inhibited 3H-PGE1 binding in the following order: 13,14-dihydro-PGE1>13,14-dihydro-15-keto-PGE1=15-keto-PGE1. The specific binding of 3H-PGE1 and 3H-PGF2 was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10−9M and a lower affinity PGE1 binding site with a Kd 1 × 10−8M. No high affinity — low capacity 3H-PGF2 sites could be demonstrated.

Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE2=16,16-dimethyl-PGE2>17-phenyl-18,19,20-trinor-P GE2>16 phenoxy-17,18,19,20-tetranor-PGE2=PGE2=PGE1=(15S)-15-methyl-PGE2>PGF2.  相似文献   


20.
Peptide II, which is encoded on a gene for a precursor protein in abdominal ganglion neurons R3-R14, was purified from extracts of abdominal ganglia of Aplysia californica. Native peptide II comigrates with synthetic standards on HPLC under isocratic conditions. Amino acid sequence and composition analyses indicate that the sequence of peptide II is Glu-Ala-Glu-Glu-Pro-Ser-Phe-Met-Thr-Arg-Leu, as predicted from the precursor. The molluscan cardioexcitatory peptide Phe-Met-Arg-Phe-amide was also identified in abdominal ganglion extracts by similar means. The large amount of peptide II recovered (100 ng/ganglion), and its location on the precursor between two pairs of basic residues, strongly suggest that the precursor is processed into peptide II and at least two other peptides. Although cells R3-R14 have been postulated to play a role in cardiovascular control, peptide II was without effect at ≤10−4 M concentrations on identified abdominal ganglion neurons, the gastroesophageal artery or the heart. The physiological role of peptide II therefore remains to be elucidated.  相似文献   

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