methyl 2-(diphenylphosphino)-4-[(4,7,10-trioxa-13-(biotinylamino)tridecylamino)carbonyl]benzoate

• 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: methyl 2-(diphenylphosphino)-4-[(4,7,10-trioxa-13-(biotinylamino)tridecylamino)carbonyl]benzoate
• 英文别名: Phosphine-biotin；methyl 4-[3-[2-[2-[3-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]propoxy]ethoxy]ethoxy]propylcarbamoyl]-2-diphenylphosphanylbenzoate
• 化学式: C₄₁H₅₃N₄O₈PS
• 分子量: 792.934
• InChiKey: ABJATKZPSPFIQY-CELQPYBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  55
• 可旋转键数：
  25
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  179
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2-(diphenylphosphino)-4-[(4,7,10-trioxa-13-(biotinylamino)tridecylamino)carbonyl]benzoate 在 sodium trioxodinitrate 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 生成 、
  参考文献：
  名称：

  Rapid and Selective Nitroxyl (HNO) Trapping by Phosphines: Kinetics and New Aqueous Ligations for HNO Detection and Quantitation

  摘要：

  Recent studies distinguish the biological and pharmacological effects of nitroxyl (HNO) from its oxidized/deprotonated product nitric oxide (center dot NO), but the lack of HNO detection methods limits the understanding its in vivo mechanisms and the identification of endogenous sources. We previously demonstrated that reaction of HNO with triarylphosphines provides aza-ylides and HNO-derived amides, which may serve as stable HNO biomarkers. We now report a kinetic analysis for the trapping of HNO by phosphines, ligations of enzyme-generated HNO, and compatibility studies illustrating the selectivity of phosphines for HNO over other physiologically relevant nitrogen oxides. Quantification of HNO using phosphines is demonstrated using an HPLC-based assay and ligations of phosphine carbamates generate HNO-derived ureas. These results further demonstrate the potential of phosphine probes for reliable biological detection and quantification of HNO.

  DOI：

  10.1021/ja203652z
• 作为产物：
  描述：

  3-(二苯基膦基)-4-(甲氧基羰基)苯甲酸 、 [3AS-(3AALPHA,4BETA,6AALPHA)]-N-[3-[2-[2-(3-氨基丙氧基)乙氧基]乙氧基]丙基]六氢-2-氧代-1H-噻吩并[3,4-D]咪唑-4-戊酰胺单(三氟乙酸)盐 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 methyl 2-(diphenylphosphino)-4-[(4,7,10-trioxa-13-(biotinylamino)tridecylamino)carbonyl]benzoate
  参考文献：
  名称：

  A cell-permeable inhibitor and activity-based probe for the caspase-like activity of the proteasome

  摘要：

  The ubiquitin-proteasome pathway degrades the majority of proteins in mammalian cells and plays an essential role in the generation of antigenic peptides presented by major histocompatibility class I molecules. Proteasome inhibitors are of great interest as research tools and drug candidates. Most work on proteasome inhibitors has focused on the inhibition of the chymotryptic-like (beta 5) sites; little attention has been paid to the inhibition of two other types of active sites, the trypsin-like (beta 2) and the caspase-like (beta 1). We report here the development of the first cell-permeable and highly selective inhibitors (4 and 5) of the proteasome's caspase-like site. The selectivity of the compounds is directly and unambiguously established by Staudinger-Bertozzi labeling of proteasome subunits covalently modified with azide-functionalized inhibitor 5. This labeling reveals that the caspase-like site of the immunoproteasome (beta 1i) is a preferred target of this compound. These compounds can be used as tools to study roles of beta 1 and beta 1i sites in generation of specific antigenic peptides and their potential role as co-targets of anti-cancer drugs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.092

文献信息

• Synthetic cofactor analogs of S-adenosylmethionine as ligatable probes of biological methylation and methods for their use
  申请人：Rajski R. Scott

  公开号：US20070161007A1

  公开（公告）日：2007-07-12

  The present invention discloses compounds and methods used to specifically target substrates of methylation by S-adenosyl-L-methionine (SAM)-dependent methyltransferases. The substrates can be peptides, single stranded nucleic acids or double stranded nucleic acids, including RNA, DNA and PNA or phospholipids. The compounds disclosed are SAM analogs that are ligated to a methylation site by the methyltransferase. Also disclosed, are reacting groups that are ligatable to the cofactor analogs and can also be used as detectable labels. The reacting group can be used to cleave the substrate providing a methylation footprint. The invention can be used clinically to determine methylation state of a gene or gene promoter such as those involved in imprinting and transcription. In some preferred embodiments, the invention includes a kit, which can include one or more suitable SAM analogs and may include one or more detectable labels. In other preferred embodiments, the invention includes a pharmaceutical composition.

  本发明揭示了化合物和方法，用于特异性靶向S-腺苷基-L-甲硫氨酸（SAM）依赖的甲基转移酶的甲基化底物。这些底物可以是肽、单链核酸或双链核酸，包括RNA、DNA和PNA或磷脂。所揭示的化合物是SAM类似物，它们通过甲基转移酶与甲基化位点连接。此外，还揭示了可与辅因子类似物连接的反应基团，也可用作可检测标记。反应基团可用于裂解底物，提供甲基化足迹。本发明可用于临床上确定基因或基因启动子的甲基化状态，例如涉及印迹和转录的基因。在一些优选实施例中，本发明包括一个试剂盒，其中可以包括一个或多个适当的SAM类似物，也可以包括一个或多个可检测标记。在其他优选实施例中，本发明包括一种制药组合物。
• Bioorthogonal labelling of 3-nitrotyrosine in peptides and proteins through diazotisation mediated azidation
  作者：John Y. Ng、Jason W. H. Wong

  DOI：10.1039/c4ob02133a

  日期：——

  A bioorthogonal method of transforming 3-nitrotyrosine to 3-azidotyrosine is described, providing new opportunities to study 3-nitrotyrosine in biological samples.

  描述了一种生物正交方法，将3-硝基酪氨酸转化为3-偶氮基酪氨酸，为研究生物样品中的3-硝基酪氨酸提供了新的机会。
• US7465544B2
  申请人：——

  公开号：US7465544B2

  公开（公告）日：2008-12-16
• Rapid and Selective Nitroxyl (HNO) Trapping by Phosphines: Kinetics and New Aqueous Ligations for HNO Detection and Quantitation
  作者：Julie A. Reisz、Charles N. Zink、S. Bruce King

  DOI：10.1021/ja203652z

  日期：2011.8.3

  Recent studies distinguish the biological and pharmacological effects of nitroxyl (HNO) from its oxidized/deprotonated product nitric oxide (center dot NO), but the lack of HNO detection methods limits the understanding its in vivo mechanisms and the identification of endogenous sources. We previously demonstrated that reaction of HNO with triarylphosphines provides aza-ylides and HNO-derived amides, which may serve as stable HNO biomarkers. We now report a kinetic analysis for the trapping of HNO by phosphines, ligations of enzyme-generated HNO, and compatibility studies illustrating the selectivity of phosphines for HNO over other physiologically relevant nitrogen oxides. Quantification of HNO using phosphines is demonstrated using an HPLC-based assay and ligations of phosphine carbamates generate HNO-derived ureas. These results further demonstrate the potential of phosphine probes for reliable biological detection and quantification of HNO.
• A cell-permeable inhibitor and activity-based probe for the caspase-like activity of the proteasome
  作者：Paul F. van Swieten、Emlyn Samuel、Rosa Orient Hernández、Adrianus M.C.H. van den Nieuwendijk、Michiel A. Leeuwenburgh、Gijsbert A. van der Marel、Benedikt M. Kessler、Herman S. Overkleeft、Alexei F. Kisselev

  DOI：10.1016/j.bmcl.2007.03.092

  日期：2007.6

  The ubiquitin-proteasome pathway degrades the majority of proteins in mammalian cells and plays an essential role in the generation of antigenic peptides presented by major histocompatibility class I molecules. Proteasome inhibitors are of great interest as research tools and drug candidates. Most work on proteasome inhibitors has focused on the inhibition of the chymotryptic-like (beta 5) sites; little attention has been paid to the inhibition of two other types of active sites, the trypsin-like (beta 2) and the caspase-like (beta 1). We report here the development of the first cell-permeable and highly selective inhibitors (4 and 5) of the proteasome's caspase-like site. The selectivity of the compounds is directly and unambiguously established by Staudinger-Bertozzi labeling of proteasome subunits covalently modified with azide-functionalized inhibitor 5. This labeling reveals that the caspase-like site of the immunoproteasome (beta 1i) is a preferred target of this compound. These compounds can be used as tools to study roles of beta 1 and beta 1i sites in generation of specific antigenic peptides and their potential role as co-targets of anti-cancer drugs. (c) 2007 Elsevier Ltd. All rights reserved.