5'-O-[(D-prolyl)-sulfamoyl]adenosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-O-[(D-prolyl)-sulfamoyl]adenosine
• 英文别名: 5'-O-[N-(d-prolyl)-sulfamoyl]-adenosine；[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2R)-pyrrolidine-2-carbonyl]sulfamate
• 化学式: C₁₅H₂₁N₇O₇S
• 分子量: 443.44
• InChiKey: LKVJEMXWEODCAY-FGOODDOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  212
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 氨基磺酰氯 、 sodium hydride 、 三氟乙酸 、 1,8-diazabicyclo-[5,4,0]-undecane 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 5'-O-[(D-prolyl)-sulfamoyl]adenosine
  参考文献：
  名称：

  Synthesis and Aminoacyl-tRNA Synthetase Inhibitory Activity of Prolyl Adenylate Analogs

  摘要：

  Two nonhydrolyzable prolyl adenylate analogs, 5'-O-[N-(L-prolyl)-sulfamoyl]adenosine (L-PSA) and 5'-O-[N-(D-prolyl)-sulfamoyl] adenosine (D-PSA), were prepared in three steps from 2',3'-di-O-isopropylideneadenosine. Both of these compounds inhibited the in vitro activity of Escherichia coli and human prolyl-tRNA synthetase (ProRS). The human enzyme used in this study was derived from the carboxy-terminal domain of the multifunctional human EPRS gene. The K-i(ATP) values for L-PSA, determined using the ATP-PPi exchange assay, are very similar for both synthetases (approximate to 1-2 nM). The K-i(Pro) values, on the other hand, vary approximately seven-fold between the two synthetases (0.6 nM for human and 4.3 nM for E. coli). The K-i values measured for the D-PSA analog are much higher (51-470 nM) for all cases examined; however, the same species-specific differences are observed with respect to K-i(Pro). These results indicate possible structural differences in or near the active sites of the two enzymes that may be exploited in the future design of compounds that function as species-specific synthetase inhibitors in vivo. (C) 1996 Academic Press, Inc.

  DOI：

  10.1006/bioo.1996.0025

文献信息

• Synthesis and Aminoacyl-tRNA Synthetase Inhibitory Activity of Prolyl Adenylate Analogs
  作者：Donald Heacock、Craig J. Forsyth、Kiyotaka Shiba、Karin Musier-Forsyth

  DOI：10.1006/bioo.1996.0025

  日期：1996.9

  Two nonhydrolyzable prolyl adenylate analogs, 5'-O-[N-(L-prolyl)-sulfamoyl]adenosine (L-PSA) and 5'-O-[N-(D-prolyl)-sulfamoyl] adenosine (D-PSA), were prepared in three steps from 2',3'-di-O-isopropylideneadenosine. Both of these compounds inhibited the in vitro activity of Escherichia coli and human prolyl-tRNA synthetase (ProRS). The human enzyme used in this study was derived from the carboxy-terminal domain of the multifunctional human EPRS gene. The K-i(ATP) values for L-PSA, determined using the ATP-PPi exchange assay, are very similar for both synthetases (approximate to 1-2 nM). The K-i(Pro) values, on the other hand, vary approximately seven-fold between the two synthetases (0.6 nM for human and 4.3 nM for E. coli). The K-i values measured for the D-PSA analog are much higher (51-470 nM) for all cases examined; however, the same species-specific differences are observed with respect to K-i(Pro). These results indicate possible structural differences in or near the active sites of the two enzymes that may be exploited in the future design of compounds that function as species-specific synthetase inhibitors in vivo. (C) 1996 Academic Press, Inc.