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Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose mimics: N-1-[(5 ′′-O-phosphorylethoxy)methyl]-5 ′-O-phosphorylinosine 5 ′,5 ′′-cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives
Gu, XF; Yang, Z; Zhang, L; Kunerth, S; Fliegert, R; Weber, K; Guse, AH; Zhang, L
刊名JOURNAL OF MEDICINAL CHEMISTRY
2004-11-04
DOI10.1021/jm040092t
47期:23页:5674-5682
收录类别SCI ; IC
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Medicinal
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]INDUCED CA2+ RELEASE ; ADENOSINE-DIPHOSPHORIBOSE CADPR ; T-LYMPHOCYTES ; CARBOCYCLIC-RIBOSE ; DIPHOSPHATE-RIBOSE ; CALCIUM-RELEASE ; CELL-LINES ; RECEPTORS ; ANALOG ; POTENT
英文摘要

N-1- [(5"-O-Phosphorylethoxy)methyl] -5′-O-phosphorylinosine 5′,5"-cyclicpyrophosphate (cIDPRE 2a) and the 8-substituted derivatives 8-bromo-, 8-azido-, 8-amino-, and 8-Cl-cIDPRE (2b-e) were synthesized from N1- [(5"-acetoxyethoxy)methyl] -2′,3′-O-isopropylideneinosine (5) in good yields. The pharmacological activities of cIDPRE and the 8-substituted derivatives (2a-e) were analyzed in intact and permeabilized. human Jurkat T-lymphocytes. The results indicate that cIDPRE permeates the plasma membrane, releases Ca2+ from an intracellular, cADPR-sensitive Ca2+ store, and subsequently initiates Ca2+ release-activated Ca2+ entry. The Ca2+-releasing activity of cIDPRE was confirmed directly in permeabilized. cells. Using time-resolved confocal Ca2+ imaging at the single cell level, the development of global Ca2+ signals starting from local small Ca2+ signals evoked by cIDPRE was observed. 8-N-3-cIDPRE 2c and 8-NH2-cIDPRE 2d were similarly effective in their agonistic activity as compared to cIDPRE 2a, showing almost indistinguishable concentration-response curves for 2a, 2c, and 2d and very similar kinetics of Ca2+ signaling. In contrast, the halogenated derivatives 8-Br- and 8-Cl-cIDPRE (2b and 2e) did not significantly elevate [Ca2+](i). Therefore, cIDPRE 2a, 8-N-3-cIDPRE 2c, and 8-NH2-cIDPRE 2d are novel membrane permeant cADPR mimic and may provide important novel tools to study cADPR-mediated Ca2+ signaling in intact cells.

语种英语
WOS记录号WOS:000224841600013
引用统计
被引频次:54[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64407
专题北京大学药学院
作者单位1.Peking Univ, Sch Pharmaceut Sci, Natl Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China
2.Univ Hamburg, Hosp Eppendorf, Ctr Med Expt, Inst Biochem & Mol Biol 1, D-20246 Hamburg, Germany
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GB/T 7714
Gu, XF,Yang, Z,Zhang, L,et al. Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose mimics: N-1-[(5 ′′-O-phosphorylethoxy)methyl]-5 ′-O-phosphorylinosine 5 ′,5 ′′-cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives[J]. JOURNAL OF MEDICINAL CHEMISTRY,2004,47(23):5674-5682.
APA Gu, XF.,Yang, Z.,Zhang, L.,Kunerth, S.,Fliegert, R.,...&Zhang, L.(2004).Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose mimics: N-1-[(5 ′′-O-phosphorylethoxy)methyl]-5 ′-O-phosphorylinosine 5 ′,5 ′′-cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives.JOURNAL OF MEDICINAL CHEMISTRY,47(23),5674-5682.
MLA Gu, XF,et al."Synthesis and biological evaluation of novel membrane-permeant cyclic ADP-ribose mimics: N-1-[(5 ′′-O-phosphorylethoxy)methyl]-5 ′-O-phosphorylinosine 5 ′,5 ′′-cyclicpyrophosphate (cIDPRE) and 8-substituted derivatives".JOURNAL OF MEDICINAL CHEMISTRY 47.23(2004):5674-5682.
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