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101.
F. Formaggio V. Moretto M. Crisma C. Toniolo B. Kaptein Q.B. Broxterman 《Chemical biology & drug design》2004,63(2):161-170
Abstract: The novel Cα‐tetrasubstituted α‐amino acid Cα‐methyl, Cα‐cyclohexylglycine was prepared by hydrogenation of its Cα‐methyl, Cα‐phenylglycine precursor. Terminally protected homodi‐, homotri‐, and homotetrapeptides from Cα‐methyl, Cα‐cyclohexylglycine and co‐oligopeptides to the pentamer level in combination with Gly or α‐aminoisobutyric acid residues were prepared by solution methods and fully characterized. The results of a conformational analysis, performed by use of Fourier transform infrared (FT‐IR) spectrophotomet absorption, 1H NMR, and X‐ray diffraction techniques, support the contention that this Cα‐methylated, Cβ‐trisubstituted aliphatic α‐amino acid is an effective β‐turn and 310‐helix inducer in tri‐ and longer peptides as its Cα‐methyl valine parent compound, but partially divergent from the corresponding aromatic Cα‐methyl, Cα‐diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers. 相似文献
102.
S. Filppula S. Yaddanapudi R. Mercier W. Xu S. Pavlopoulos A. Makriyannis 《Chemical biology & drug design》2004,64(6):225-236
Abstract: The cannabinergic system is present in a variety of organs and tissues that perform a wide range of essential physiologic functions making it an inherently important therapeutic target for drug discovery. In order to augment our knowledge regarding the interactions between cannabinoid receptors (CBs) and their ligands, efficient and effective tools are essential for robust expression and purification of these membrane‐bound proteins. In this report, we describe a suitable method for purification of the human cannabinoid receptor 2 (CB2) to a qualitative and quantitative level sufficient for mass spectral analysis. We utilized a baculovirus expression system, incorporating several epitope tags to facilitate purification and to ameliorate the effect the tags have on CB2 expression and function. Expressed protein encoded by a carboxy (C)‐terminal His‐tagged CB2 construct displayed a Bmax value of 9.3 pmol/mg with a KD of 7.30 nm using [3H]CP–55940, a standard cannabinoid radioligand, and was selected for subsequent purification experiments. Western blot analysis of purified membrane protein yielded several forms of CB2, the most abundant being a 41 kDa peptide. A second protein species was observed with an apparent molecular weight of 46 kDa representing a glycosylated form of CB2. In addition, a CB2 homodimer was also identified. The purified receptor was subjected to mass spectroscopic analysis to confirm its identity and purity. Mass spectra corresponding to the intracellular, extracellular and transmembrane domains were obtained. These experiments exemplify the importance of high‐level expression systems when developing membrane‐bound protein purification strategies. This work will aid in the identification of receptor–ligand binding sites, the characterization of molecular features involved in receptor activation, and the elucidation of the CB2 receptor tertiary structure. 相似文献
103.
从云南美登木共生放线菌菌株(Streptomyces sp.)CS的发酵产物中分离得一个新的多羟基环己烷衍生物,并通过波谱学特征鉴定化合物的结构为1-isobutyroxymethyl cyclohex-1(6)-ene-2,3,4,5-tetrol-2-isobutyrate. 相似文献
104.
Claire Joqueviel Véronique Gilard Robert Martino Myriam Malet-Martino Ulf Niemeyer 《Cancer chemotherapy and pharmacology》1997,40(5):391-399
Phosphorus-31 nuclear magnetic resonance spectroscopy was used to evaluate the stability of carboxycyclophosphamide (CXCP)
and carboxyifosfamide (CXIF) in human urine at pH 7.0 and 5.5 at 25°, 8°, −20°, and −80 °C. At 25 °C and pH 7.0, CXCP and
CXIF are relatively stable (≈10% degradation in 24 h). In contrast, they are much less stable at pH 5.5 (≈80% degradation
of CXIF and ≈50% degradation of CXCP in 24 h). The rate of degradation of CXCP and CXIF was a function of the storage temperature
of the urine samples but, even at −80 °C, was not negligible: ≈30% degradation for CXCP irrespective of pH and ≈40% and 50%
degradation for CXIF at pH 7.0 and 5.5, respectively, after storage for 6 months. CXCP was more stable than CXIF at either
pH (7.0 or 5.5) and at all storage temperatures (8°, −20°, or −80 °C) of the urine samples. CXCP and CXIF were more stable
at pH 7.0 than at pH 5.5, although this difference fell with decreasing temperatures to be almost negligible at −80 °C. To
ensure a true estimate of CXCP and CXIF levels, urine samples must be frozen and stored at −80 °C within a few hours of micturition.
CXCP and CXIF assays should also be carried out within 2 months and 1 month of storage, respectively.
Received: 13 July 1996 / Accepted: 20 January 1997 相似文献
105.
Ben-Yoseph Oded Lyons John C. Song Chang W. Ross Brian D. 《Journal of neuro-oncology》1998,36(2):149-157
Malignant gliomas have been associated with a high rate of glycolytic activity which is believed necessary to sustain cellular function and integrity. Since lonidamine (LND) is believed to reduce tumor glucose utilization by inhibition of the mitochondrially-bound glycolytic enzyme hexokinase (HK), 31P magnetic resonance spectroscopy (MRS) was used to noninvasively follow the effects of LND on both tumor pH and the high-energy phosphate metabolites; ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) in subcutaneous rat 9L gliosarcomas. 31P tumor spectra acquired in 5 min intervals pre- and post LND administration of 50 and 100 mg/kg, i.p. revealed an acidotic pH shift of – 0.25 and – 0.45 pH units, respectively within 30 min post administration. The ATP/Pi ratio of 9L tumors decreased to 40% of control and Pi levels increased to 280% of control over a 3 hr period. LND exerted no effect on tumor blood flow and mean arterial blood pressure. Brain and muscle metabolite levels and pH were also unaffected by LND. In vitro measurements of cultured 9L tumor cell intra- and extracellular lactate, pentose phosphate pathway (PPP) and hexokinase (HK) activities suggest that the mode of action of LND involves inhibition of lactate efflux and intracellular acidification. The selective reduction of tumor energy metabolites and pH by LND may be exploitable for sensitizing gliomas to radiation, chemotherapy or hyperthermia. 相似文献
106.
PURPOSE: Hippocampal neuron loss and associated memory deficits are characteristic of intractable temporal lobe epilepsy (TLE). Proton chemical shift imaging (CSI) spectroscopy is a sensitive tool for detecting neuronal loss. The aim of this study was to investigate the correlation between memory functions and results provided by CSI spectroscopy of the hippocampal structures. METHODS: Ten patients with cryptogenic TLE participated. The study protocol involved both the acquisition of high-spatial-resolution CSI spectroscopy and neuropsychological evaluation, including memory testing and intracarotid sodium amytal test (IAT). The analysis of the CSI data was based on normative data obtained in 30 healthy volunteers. Memory functions were represented by verbal, visual, and general memory indices. RESULTS: A significant correlation was found between CSI spectroscopy of the hippocampal formation and the verbal memory indices for the dominant hemisphere. In addition, there was a significant correspondence of the qualitative judgment "hippocampal pathology indicated by CSI spectroscopy" and both "material specific memory deficit" and "memory deficit in the IAT." CONCLUSIONS: Our results demonstrate that CSI spectroscopy of the hippocampal structures is strongly related to lateralized memory deficits in patients with TLE. This suggests that CSI spectroscopy may be useful in the prediction of postoperative outcome in respect of seizure control and memory. 相似文献
107.
运用共振拉曼散射光谱法测定皮肤类胡萝卜素 总被引:1,自引:1,他引:1
[目的]用共振拉曼散射光谱法测试皮肤类胡萝卜素水平,观察机体类胡萝卜素变化情况。[方法]120名成年受试者按照其年龄、性别和试验前皮肤类胡萝卜素指数配对后,随机分为试验组和对照组。试验组人群每天补充β-胡萝卜素12.6mg,共8周。两组人群在试验前、试验第4周末和第8周末,分别运用共振拉曼散射光谱测试受试者皮肤类胡萝卜素,观察皮肤中类胡萝卜素水平变化情况。同时进行膳食调查,了解膳食摄入情况。[结果]试食组人群补充β-胡萝卜素第4周时皮肤类胡萝卜素指数比试验前的基础值上升了24.3%、第8周时比试验前的基础值上升了44.0%,且与对照人群相比差异有统计学意义(P<0.001)。[结论]由于两组人群在试验期间的膳食摄入情况没有差异,实验中试食组人群皮肤类胡萝卜素指数的增高可认为与补充β-胡萝卜素有关。共振拉曼散射光谱作为一种非创伤性的检测方法,可用于反映皮肤类胡萝卜素水平,进而提示机体类胡萝卜素的营养状况。 相似文献
108.
109.
目的研究琥珀酸胆固醇酯(CHEMS)对二棕榈酰磷脂酰胆碱(DPPC)脂质体的膜稳定作用以及作用机制;以CHEMS和DPPC为膜材制备柴胡皂苷-D(SSD)脂质体,考察其包封率和溶血性。方法差示扫描量热法(DSC)和荧光释放实验考察CHEMS的膜稳定作用,傅立叶红外(FT-IR)研究CHEMS与DPPC膜的作用机制,沉降实验研究CHEMS与SSD相互作用,溶血实验考察了以CHEMS为膜材包裹SSD脂质体的溶血性。结果CHEMS在膜稳定性上优于胆固醇(CHOL),CHEMS与DPPC的极性端头同时有氢键和静电作用;CHEMS与SSD不会形成不溶性复合物(INCOM),用DPPC和CHEMS为膜材制备了稳定的SSD包裹的脂质体,其溶血性大大降低。结论CHEMS对DPPC膜的稳定作用大于CHOL,并可取代CHOL作为制备胆固醇依赖性的溶血性皂苷脂质体的膜稳定剂。 相似文献
110.
Andrea Bernini Ottavia Spiga Arianna Ciutti Maria Scarselli Giuseppe Bottoni Paolo Mascagni Neri Niccolai 《European journal of pharmaceutical sciences》2004,22(5):445-450
A 1H and 13C NMR study on the inclusion complex of paroxetine with β-cyclodextrin was carried out in order to define the stoichiometry of the association and its strength. Proton and carbon chemical shift measurements of paroxetine and β-cyclodextrin were performed at several molar ratios and temperatures, allowing the determination of a 1:1 stoichiometry and an association constant value of the order of 2 × 103 for the paroxetine–β-cyclodextrin complex. Overhauser effects in the rotating frame were also measured, and the experimental interproton distance constraints have been used for molecular model building of the complex. The obtained model indicates that the benzodioxolyl moiety of paroxetine is deeply inserted in the cavity of the cylindrical structure of β-cyclodextrin, while the fluoro-phenyl ring lays above the wider rim. 相似文献