2-[(6-biotinylamido)hexylthio]adenosine 5'-triphosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2-[(6-biotinylamido)hexylthio]adenosine 5'-triphosphate
• 英文别名: [[(2R,3S,4R,5R)-5-[2-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexylsulfanyl]-6-aminopurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
• 化学式: C₂₆H₄₃N₈O₁₅P₃S₂
• 分子量: 864.725
• InChiKey: QVWIUCJHVJISDX-DGWADGOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  54
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  400
• 氢给体数：
  10
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  2-[(6-aminohexyl)thio]adenosine 5'-triphosphate tetrabutylammonium 、 (+)生物素-N-琥珀酰亚胺基酯 以 二甲基亚砜 、 乙腈 为溶剂， 反应 3.0h， 以62%的产率得到2-[(6-biotinylamido)hexylthio]adenosine 5'-triphosphate
  参考文献：
  名称：

  Novel modified adenosine 5′-triphosphate analogues pharmacologically characterized in human embryonic kidney 293 cells highly expressing rat brain P2Y1 receptor:

  摘要：

  Rat brain P2Y(1) (rP2Y(1)) receptor-transfected human embryonic kidney cells (HEK 293) were recently shown to have enhanced reactivity to both ATP and ADP (Vohringer C, Schafer R, Reiser G. Biochem Pharmacol 2000;59:791-800). Here, we demonstrated the usefulness of this cell line as a system for further studying novel adenine nucleotide analogues (Halbfinger et al. J Med Chem 1999;42:5325-37) and for the biochemical characterization of the P2Y(1) receptor. By measurement of intracellular Ca2+ release, for 2-butylthio-, 2-butylamino-, and 2-butyloxy-ATP (2-BuS-, 2-BuNH-, 2-BuO-ATP), EC50 values of 1.3, 5, and 60 nM were determined, markedly lower than the value for ATP (130 nM). The EC50 for 2-BuSADP was 1.1 nM. The corresponding 8-substituted ATP analogues showed a substantially lower potency than ATP (ATP > 8-BuSATP > 8-BuNHATP approximate to 8-BuOATP). AMP induced intracellular Ca2+ release with a very low potency; 2- and 8-substitutions on AMP caused no significant potency shift, except for 2-BuSAMP (EC50 = 180 nM). Another new P2Y receptor probe, 2-[(6-biotinylamido)-hexylthio]ATP, was 22-fold more potent than ATP (EC50 = 6 nM). revealing that even more bulky substituents linked to the C-2 position bind with high affinity at the P2Y(1) receptor. This biotinylated probe was successfully used for the enrichment of the P2Y(1) receptor tagged with green fluorescent protein from a crude membrane fraction. This one-step enrichment provides a substantial advance for P2Y(1) receptor purification. Thus, human embryonic kidney 293 cells stably transfected with the rP2Y(1) receptor represent a powerful model system for pharmacological characterization of the P2Y(1) receptor, circumventing problems associated with natural systems. They provide a means for the development of P2Y(1) ligands of high potency and a good source for obtaining purified P2Y(1) receptor. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0006-2952(01)00593-7

文献信息

• Novel modified adenosine 5′-triphosphate analogues pharmacologically characterized in human embryonic kidney 293 cells highly expressing rat brain P2Y1 receptor:
  作者：Gregor Zündorf、Rainer Schäfer、Christian Vöhringer、Efrat Halbfinger、Bilha Fischer、Georg Reiser

  DOI：10.1016/s0006-2952(01)00593-7

  日期：2001.5

  Rat brain P2Y(1) (rP2Y(1)) receptor-transfected human embryonic kidney cells (HEK 293) were recently shown to have enhanced reactivity to both ATP and ADP (Vohringer C, Schafer R, Reiser G. Biochem Pharmacol 2000;59:791-800). Here, we demonstrated the usefulness of this cell line as a system for further studying novel adenine nucleotide analogues (Halbfinger et al. J Med Chem 1999;42:5325-37) and for the biochemical characterization of the P2Y(1) receptor. By measurement of intracellular Ca2+ release, for 2-butylthio-, 2-butylamino-, and 2-butyloxy-ATP (2-BuS-, 2-BuNH-, 2-BuO-ATP), EC50 values of 1.3, 5, and 60 nM were determined, markedly lower than the value for ATP (130 nM). The EC50 for 2-BuSADP was 1.1 nM. The corresponding 8-substituted ATP analogues showed a substantially lower potency than ATP (ATP > 8-BuSATP > 8-BuNHATP approximate to 8-BuOATP). AMP induced intracellular Ca2+ release with a very low potency; 2- and 8-substitutions on AMP caused no significant potency shift, except for 2-BuSAMP (EC50 = 180 nM). Another new P2Y receptor probe, 2-[(6-biotinylamido)-hexylthio]ATP, was 22-fold more potent than ATP (EC50 = 6 nM). revealing that even more bulky substituents linked to the C-2 position bind with high affinity at the P2Y(1) receptor. This biotinylated probe was successfully used for the enrichment of the P2Y(1) receptor tagged with green fluorescent protein from a crude membrane fraction. This one-step enrichment provides a substantial advance for P2Y(1) receptor purification. Thus, human embryonic kidney 293 cells stably transfected with the rP2Y(1) receptor represent a powerful model system for pharmacological characterization of the P2Y(1) receptor, circumventing problems associated with natural systems. They provide a means for the development of P2Y(1) ligands of high potency and a good source for obtaining purified P2Y(1) receptor. (C) 2001 Elsevier Science Inc. All rights reserved.