6-hydroxymethylpterin monophosphate | 49754-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 6-hydroxymethylpterin monophosphate
• 英文别名: 6-Hydroxymethyl-pterin-monophosphat；phosphoric acid mono-(2-amino-4-oxo-3,4-dihydro-pteridin-6-ylmethyl) ester；Pterin-6-Yl-Methyl-Monophosphate；(2-amino-4-oxo-3H-pteridin-6-yl)methyl dihydrogen phosphate
• CAS: 49754-41-8
• 化学式: C₇H₈N₅O₅P
• 分子量: 273.145
• InChiKey: AJXFJEHKGGCFNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氨基-4-羟基蝶啶-6-甲醛 在 sodium tetrahydroborate 、 磷酸 作用下， 反应 4.0h， 生成 6-hydroxymethylpterin monophosphate
  参考文献：
  名称：

  Bisubstrate Analogue Inhibitors of 6-Hydroxymethyl-7,8-dihydropterin Pyrophosphokinase:  Synthesis and Biochemical and Crystallographic Studies

  摘要：

  6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to the biosynthesis of folate cofactors. Like other enzymes in the folate pathway, HPPK is an ideal target for the development of antimicrobial agents because the enzyme is essential for microorganisms but is absent from human and animals. Three bisubstrate analogues have been synthesized for HPPK and characterized by biochemical and X-ray crystallographic analyses. All three bisubstrate analogues consist of a pterin, an adenosine moiety, and a link composed of 2-4 phosphoryl groups. P-1-(6-Hydroxymethylpterin)-P-2-(5 ' -adenosyl)diphosphate (HP(2)A, 5) shows little affinity and inhibitory activity for E. coli HPPK, P-1-(6-Hydroxymethylpterin)-P-4-(5 ' -adenosyl)triphosphate (H(P)3A, 6) shows moderate affinity and inhibitory activity with K-d = 4.25 muM in the presence of Mg2+ and IC50 = 1.27 muM. P-1-(6-Hydroxymethylpterin)-P-4-(5 ' -adenosyl)tetraphosphate (HP(4)A, 7) shows the highest affinity and inhibitory activity with K-d = 0.47 muM in the presence of Mg2+ and IC50 = 0.44 muM The affinity of MgHP(4)A for HPPK is similar to 116 and 76 times higher than that of MgADP and 6-hydroxymethylpterin, respectively. The crystal structure of HPPK in complex with 7 (HPPK MgHP4A) has been determined at 1.85 Angstrom resolution with a crystallographic R factor of 0.185. The crystal structure shows that 7 occupies both HP- and ATP-binding sites and induces significant conformational changes in HPPK. The biochemical and structural studies of the bisubstrate analogues indicate that the bisubstrate analogue approach can produce more potent inhibitors for HPPK and the minimum length of the link for a bisubstrate analogue is similar to7 Angstrom.

  DOI：

  10.1021/jm0004493

文献信息

• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• ADVANCED DRUG DEVELOPMENT AND MANUFACTURING
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519A2

  公开（公告）日：2009-08-05
• X-RAY FLUORESCENCE ANALYSIS METHOD
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519B1

  公开（公告）日：2012-08-01
• X-ray microscope
  申请人：XRpro Sciences, Inc.

  公开号：EP2511844B1

  公开（公告）日：2015-08-12
• METHODS OF DETECTION USING X-RAY FLUORESCENCE
  申请人：Icagen, Inc.

  公开号：EP3681504A1

  公开（公告）日：2020-07-22