2-[[[3-[[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]amino]-3-carboxypropyl]hydroxyphosphinyl]methyl]pentane-1,5-dioic acid | 1190871-10-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[[[3-[[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]amino]-3-carboxypropyl]hydroxyphosphinyl]methyl]pentane-1,5-dioic acid
• CAS: 1190871-10-3
• 化学式: C₂₄H₂₈N₇O₁₀P
• 分子量: 605.501
• InChiKey: WZCMBUXAEOKHBI-VYIIXAMBSA-N

反应信息

• 作为反应物：
  描述：

  2-[[[3-[[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]amino]-3-carboxypropyl]hydroxyphosphinyl]methyl]pentane-1,5-dioic acid 在 sodium dithionite 、 2-巯基乙醇 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 1.33h， 生成
  参考文献：
  名称：

  Characterisation of the bifunctional dihydrofolate synthase–folylpolyglutamate synthase from Plasmodium falciparum; a potential novel target for antimalarial antifolate inhibition

  摘要：

  Unusually for a eukaryote, the malaria parasite Plasmodium falciparum expresses dihydrofolate synthase (DHFS) and folylpolyglutamate synthase (FPGS) as a single bifunctional protein. The two activities contribute to the essential pathway of folate biosynthesis and modification. The DHFS activity of recombinant PfDHFS-FPGS exhibited non-standard kinetics at high co-substrate (glutamate and ATP) concentrations, being partially inhibited by increasing concentrations of its principal substrate, dihydropteroate (DHP). Binding of DHP to the catalytic and inhibitory sites exhibited dissociation constants of 0.50 mu M and 1.25 mu M, respectively. DHFS activity measured under lower co-substrate concentrations, where data fitted the Michaelis-Menten equation, yielded apparent K-m values of 0.88 mu M for DHP, 22.8 mu M for ATP and 5.97 mu M for glutamate. Of the substrates tested in FPGS assays, only tetrahydrofolate (THF) was efficiently converted to polyglutamylated forms, exhibiting standard kinetics with an apparent K-m of 0.96 mu M; dihydrofolate, folate and the folate analogue methotrexate (MTX) were negligibly processed, emphasising the importance of the oxidation state of the pterin moiety. Moreover. MIX inhibited neither DHFS nor FPGS, even at high concentrations. Conversely, two phosphinate analogues of 7,8-dihydrofolate that mimic tetrahedral intermediates formed during DHFS- and FPGS-catalysed glutamylation were powerfully inhibitory. The k(i) value of an aryl phosphinate analogue against DHFS was 0.14 mu M and for an alkyl phosphinate against FPGS 0.091 mu M, with each inhibitor showing a high degree of specificity. This, combined with the absence of DHFS activity in humans, suggests PfDHFS-FPGS might represent a potential new drug target in the previously validated folate pathway of P. falciparum. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molbiopara.2010.03.012