Farnesyl methylene diphosphonate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: Farnesyl methylene diphosphonate
• 英文别名: all-trans farnesyl diphosphate；all-trans FPP；Farnesyl methylenediphosphonate；[hydroxy-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienoxy]phosphoryl]methylphosphonic acid
• 化学式: C₁₆H₃₀O₆P₂
• 分子量: 380.358
• InChiKey: ROIDNMZVDQIXIS-XGGJEREUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dansyl-GCVLS 、 Farnesyl methylene diphosphonate 在 rat protein farnesyltransferase 作用下， 生成 dansyl-G(S-farnesyl)CVLS
  参考文献：
  名称：

  Synthesis of acyloxymethyl ester prodrugs of the transferable protein farnesyl transferase substrate farnesyl methylenediphosphonate

  摘要：

  Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.017

文献信息

• Use of analogues of polyisoprenyl pyrophosphate for inhibiting protein isoprenylation
  申请人：NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIJK ONDERZOEK TNO

  公开号：EP0540782A1

  公开（公告）日：1993-05-12

  The invention provides the use of a polyisoprenyl pyrophosphate analogue for preparing a pharmaceutical composition suitable for inhibiting protein isoprenylation. The polyisoprenyl pyrophosphate analogue may have formula 1, wherein: Pren represents a C₁₀-C₃₀ terpenoid group or a derivative thereof; A¹, A², A³ and A⁴ independently represent a direct bond or a C₁-C₄ alkylene or alkenylene group, optionally substituted; X¹, X², X³ and X⁴ independently represent a direct bond, oxygen, sulphur, imino or methylimino; Y¹, Y² and Y³ independently represent hydroxy, alkoxy, mercapto, alkylthio, amino, mono- or di-alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, aryl or arylalkyl, whereby one of Y¹, Y² and Y³ may also represent a C₇-C₃₀ alkyl or alkenyl group; Z¹ and Z² independently represent oxygen or sulphur; and n is 0, 1 or 2, preferably 1; or a pharmaceutically acceptable salt thereof. The pharmaceutical composition is suitable for the prophylaxis and/or treatment of carcinomas and for the inhibition of the isoprenylation of a ras protein.

  本发明提供了一种多异戊烯基焦磷酸盐类似物，用于制备适用于抑制蛋白质异戊烯化的药物组合物。多异戊烯基焦磷酸酯类似物可具有式 1、 其中 Pren 代表 C₁₀-C₃₀萜类基团或其衍生物； A¹、A²、A³和 A⁴各自代表直接键或任选被取代的 C₁-C₄亚烷基或烯基； X¹、X²、X³ 和 X⁴ 各自代表直接键、氧、硫、亚氨基或甲基亚氨基； Y¹、Y² 和 Y³ 独立地代表羟基、烷氧基、巯基、烷硫基、氨基、单或双烷基氨基、烷基、烯基、炔基、环烷基、芳基或芳烷基，其中 Y¹、Y² 和 Y³ 还可以代表 C₇-C₃₀ 烷基或烯基； Z¹ 和 Z² 各自代表氧或硫；以及 n 为 0、1 或 2，优选 1； 或其药学上可接受的盐。 该药物组合物适用于预防和/或治疗癌症以及抑制 ras 蛋白的异戊烯化。
• A novel geranylgeranyl reductase from the methanogenic archaeon<i>Methanosarcina acetivorans</i>displays unique regiospecificity
  作者：Takuya Ogawa、Keisuke Isobe、Takeshi Mori、Susumu Asakawa、Tohru Yoshimura、Hisashi Hemmi

  DOI：10.1111/febs.12851

  日期：2014.7

  Saturation of a prenyl group to various levels is a frequently observed modification of isoprenoids. The members of the geranylgeranyl reductase family, however, are the only known enzymes responsible for such reductive modifications in archaea. A methanogenic archaeon, Methanosarcina acetivorans, has proteins homologous to phytoene desaturase CrtI, which is the carotenogenic enzyme that catalyzes oxidation/isomerization of phytoene to lycopene, but their function in carotenogenesis is unlikely in a methanogen that does not produce carotenoids. In the present study, we identified one of the homologues, MA1492, as a new type of archaeal geranylgeranyl reductase that is not homologous to known geranylgeranyl reductases. The expression of MA1492 in Escherichia coli cells, which were genetically modified to produce unsaturated archaeal‐type lipids, led to the production of partially saturated lipid derivatives. Furthermore, we analyzed the substrate specificity of recombinant MA1492 via in vitro assays. The LC‐MS, or radio‐TLC, analysis of the reaction products showed that the enzyme was definitely specific to compounds containing C20 geranylgeranyl groups and reduced only one of four double bonds in a geranylgeranyl chain. The GC‐MS analysis of the product from geranylgeraniol confirmed that the reduction selectively occurred on the ω‐terminal double bond. The available crystallographic structure of an orthologue enzyme may explain the reaction mechanism that achieves the substrate specificity and regiospecificity.DatabaseMicrobial Genome Database (http://mbgd.genome.ad.jp/), EMBOSS Needle (https://www.ebi.ac.uk/Tools/psa/emboss_needle)
• US5827838A
  申请人：——

  公开号：US5827838A

  公开（公告）日：1998-10-27
• US7745589B1
  申请人：——

  公开号：US7745589B1

  公开（公告）日：2010-06-29
• Synthesis of acyloxymethyl ester prodrugs of the transferable protein farnesyl transferase substrate farnesyl methylenediphosphonate
  作者：Jerry M. Troutman、Kareem A.H. Chehade、Katarzyna Kiegiel、Douglas A. Andres、H. Peter Spielmann

  DOI：10.1016/j.bmcl.2004.07.017

  日期：2004.10

  Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs. (C) 2004 Elsevier Ltd. All rights reserved.