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71.
A short and straightforward synthesis of DAMGO is described. 相似文献
72.
《合成通讯》2013,43(15):2605-2611
Abstract The o-nitrobenzyl group, possessing distinct advantage of being photolabile under mild conditions, was successfully connected to 8-(5,6-epoxynorbornan-2-yl)-1,3-dipropylxanthine (5), a high specific A1 adenosine receptor antagonist. The resulting compound 4 would have potential use as a prodrug. 相似文献
73.
Filip Botha Jan Budka Václav Eigner Oldřich Hudeček Lukáš Vrzal Ivana Císařová Pavel Lhoták 《Tetrahedron》2014
A new type of calixarene-based receptor designed for the recognition of chiral anions was prepared by the introduction of (S)-2-methylbutan-1-ol moieties into the lower rim of calixarene. The immobilization of calixarene skeleton in the 1,3-alternate conformation enabled the construction of a cavity consisting of preorganised ureido functions and chiral substituents in close proximity. This cavity is capable of chiral discrimination of selected anions as demonstrated on d- and l-phenylalaninates. 相似文献
74.
75.
运用分子动力学模拟,研究了腺苷酸(激动剂)与A2AAR腺苷受体蛋白的相互作用和配体结合诱导的蛋白动力学变化.识别了与腺苷酸结合力强于0.5kcal/mol的关键基团:A63^2.61,I66^2.64,V84^3.32,L85^3.33,T88^3.36,F168^5.29,M177^5.38,L249^6.51,H250^6.52和N253^6.55,观察到腺苷酸没有与L167^5.28相互作用,这一结果支持了L167^5.28是抑制剂特异性结合位点,不与激动剂结合.未结合配体(激动剂或抑制剂)的单体A2AAR和腺苷酸结合后的A2AAR在构象上有三个不同功能性开关.腺苷酸结合可以诱导A2AAR腺苷受体蛋白的构象调整,使得三个功能性开关器件的构象与单体A2AAR不同. 相似文献
76.
Photoaffinity cross-linking is a fast developing technology for biomolecular interactions,including receptor-ligand binding.The chemical mechanisms of the most commonly used photoactivatable probes and their respective photochemistry are summarized.This review focuses on the expanding utilities of this technology as a result of recent advances in the(i)identification of receptor contact sites,(ii)monitoring ligand-induced receptor conformational changes,(iii)identification of global binding surfaces,(iv)binding mode analysis using bifunctional photo-probes,(v)application of biosynthetic photo-probes,and(vi)examples of novel target discovery using this technology.Limitations and future potential of this approach are also discussed. 相似文献
77.
Malte Behrends Charlotta Wallinder Anna Wieckowska Marie-Odile Guimond Anders Hallberg Nicole Gallo-Payet Mats Larhed 《ChemistryOpen》2014,3(2):65-75
A novel series of ligands for the recombinant human AT2 receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)6] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with Ki values in the low micromolar range versus the recombinant human AT2 receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs. 相似文献
78.
Jia Fu Qianqian Jia Peida Liang Saisai Wang Huaxin Zhou Liyang Zhang Hong Wang Chunlei Gao Yanni Lv Shengli Han Langchong He 《Journal of separation science》2022,45(14):2498-2507
Cell membrane chromatography is an effective method for screening bioactive components acting on specific receptors in complex systems, which maintains the biological activity of the membrane receptors and improves screening efficiency. However, traditional cell membrane chromatography suffers from poor stability, resulting in a limited life span and low reproducibility, greatly limiting the application of this method. To address this problem, cyanuric chloride-decorated silica gel was used for the covalent immobilization of the cell membranes. Cyanuric chloride reacts with amino groups on the cell membranes and membrane receptors to form covalent bonds. In this way, the cell membranes are not easy to fall off. The column life of the cyanuric chloride-decorated epidermal growth factor receptor/cell membrane chromatography column was extended to more than 8 days, whereas the column life of the normal cell membrane chromatography column dropped sharply in the first 3 days. A cyanuric chloride-decorated epidermal growth factor receptor/cell membrane chromatography online HPLC-IT-TOF-MSn system was applied for screening drug leads from Trifolium pratense L. One potential drug lead, formononetin, which acts on the epidermal growth factor receptor, was screened. Our strategy of covalently immobilizing cell membrane receptors also improved the stability of cell membrane chromatography. 相似文献
79.
Jun-Jie Shi Qi-Hui Jiang Tian-Ning Zhang Hao Sun Wen-Wen Shi Hendra Gunosewoyo Fan Yang Jie Tang Tao Pang Li-Fang Yu 《Molecules (Basel, Switzerland)》2021,26(5)
Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound’s safety profile and blood–brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted. 相似文献
80.
Eui-Baek Byun Ha-Yeon Song Woo Sik Kim Jeong Moo Han Ho Seong Seo Woo Yong Park Kwangwook Kim Eui-Hong Byun 《Molecules (Basel, Switzerland)》2021,26(6)
Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1. 相似文献