6-(fluorescein-5-carboxamido)hexanoic acid succinimidyl ester | 148356-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-(fluorescein-5-carboxamido)hexanoic acid succinimidyl ester
• 英文别名: 5(6)-Sfx,SE；(2,5-dioxopyrrolidin-1-yl) 6-[(3',6'-dihydroxy-1-oxospiro[2-benzofuran-3,9'-xanthene]-5-carbonyl)amino]hexanoate
• CAS: 148356-01-8
• 化学式: C₃₁H₂₆N₂O₁₀
• 分子量: 586.555
• InChiKey: OEKZTXDDIMSZIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  169
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-(fluorescein-5-carboxamido)hexanoic acid succinimidyl ester 、 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以7.2 mg的产率得到2-diethanolamino-4,8-diheptamethyleneimino-6-[(N-6-(fluorescein-6-carboxamido)-hexanoylaminoethyl)-ethanolamino]-pyrimido[5,4-d]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of 2-Diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein Conjugate (8MDP-fluor), As a Novel Equilibrative Nucleoside Transporter Probe

  摘要：

  Nucleoside transporters are integral membrane glycoproteins that play critical roles in physiological nucleoside and nucleobase fluxes, and influence the efficacy of many nucleoside chemotherapy drugs. Fluorescent reporter ligands/substrates have been shown to be useful in the analysis of nucleoside transporter (NT) protein expression and discovery of new NT inhibitors. In this study, we have developed a novel dipyridamole (DP)-based equilibrative nucleoside transporter 1 (ENT1) fluorescent probe. The potent ENT1 and ENT2 inhibitor analogue of dipyridamole, 2,6-bis(diethanolamino)-4,8-diheptamethyleneiminopyrimido[5,4-d]pyrimidine (4, 8MDP), was modified to replace one beta-hydroxyethyl group of the amino substituent at the 2-position with a beta-aminoethyl group and then conjugated through the amino group to 6-(fluorescein-5carboxamido)hexanoyl moiety to obtain a new fluorescent molecule, 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate, designated 8MDP-fluorescein (8MDP-fluor, 6). The binding affinities of 8MDP-fluor at ENT1 and ENT2 are reflected by the uridine uptake inhibitory K(i) values of 52.1 nM and 285 nM, respectively. 8MDP-fluor was successfully demonstrated to be a flow cytometric probe for ENT1 comparable to the nitrobenzylmercaptopurine riboside (NBMPR) analogue ENT1 fluorescent probe SAENTA-X8-fluorescein (SAENTA-fluor, 1). This is the first reported dipyridamole-based ENT1 fluorescent probe, which adds a novel tool for probing ENT1, and possibly ENT2.

  DOI：

  10.1021/bc2000758

文献信息

• Design, Synthesis, and Evaluation of 2-Diethanolamino-4,8-diheptamethyleneimino-2-(<i>N</i>-aminoethyl-<i>N</i>-ethanolamino)-6-(<i>N,N</i>-diethanolamino)pyrimido[5,4-<i>d</i>]pyrimidine-fluorescein Conjugate (8MDP-fluor), As a Novel Equilibrative Nucleoside Transporter Probe
  作者：Wenwei Lin、John K. Buolamwini

  DOI：10.1021/bc2000758

  日期：2011.6.15

  Nucleoside transporters are integral membrane glycoproteins that play critical roles in physiological nucleoside and nucleobase fluxes, and influence the efficacy of many nucleoside chemotherapy drugs. Fluorescent reporter ligands/substrates have been shown to be useful in the analysis of nucleoside transporter (NT) protein expression and discovery of new NT inhibitors. In this study, we have developed a novel dipyridamole (DP)-based equilibrative nucleoside transporter 1 (ENT1) fluorescent probe. The potent ENT1 and ENT2 inhibitor analogue of dipyridamole, 2,6-bis(diethanolamino)-4,8-diheptamethyleneiminopyrimido[5,4-d]pyrimidine (4, 8MDP), was modified to replace one beta-hydroxyethyl group of the amino substituent at the 2-position with a beta-aminoethyl group and then conjugated through the amino group to 6-(fluorescein-5carboxamido)hexanoyl moiety to obtain a new fluorescent molecule, 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate, designated 8MDP-fluorescein (8MDP-fluor, 6). The binding affinities of 8MDP-fluor at ENT1 and ENT2 are reflected by the uridine uptake inhibitory K(i) values of 52.1 nM and 285 nM, respectively. 8MDP-fluor was successfully demonstrated to be a flow cytometric probe for ENT1 comparable to the nitrobenzylmercaptopurine riboside (NBMPR) analogue ENT1 fluorescent probe SAENTA-X8-fluorescein (SAENTA-fluor, 1). This is the first reported dipyridamole-based ENT1 fluorescent probe, which adds a novel tool for probing ENT1, and possibly ENT2.