5-(Methylsulfonylthio)pentanoic acid | 92953-14-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-(Methylsulfonylthio)pentanoic acid
• 英文别名: 5-[(Methylsulfonyl)thio]pentanoic acid；5-methylsulfonylsulfanylpentanoic acid
• CAS: 92953-14-5
• 化学式: C₆H₁₂O₄S₂
• 分子量: 212.291
• InChiKey: UVKIQKSQWZXOGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(Methylsulfonylthio)pentanoic acid 在 4-甲基苯磺酸吡啶 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.03h， 生成 S-(5-(hydroxyamino)-5-oxopentyl)methanesulfonothioate
  参考文献：
  名称：

  Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A

  摘要：

  Botulinum neurotoxins have remarkable persistence (similar to weeks to months in cells), outlasting the small-molecule inhibitors designed to target them. To address this disconnect, inhibitors bearing two pharmacophores.a zinc binding group and a Cys-reactive warhead.were designed to leverage both affinity and reactivity. A series of first-generation bifunctional inhibitors was achieved through structure-based inhibitor design. Through X-ray crystallography, engagement of both the catalytic Zn2+ and Cys165 was confirmed. A second-generation series improved on affinity by incorporating known reversible inhibitor pharmacophores; the mechanism was confirmed by exhaustive dialysis, mass spectrometry, and in vitro evaluation against the C165S mutant. Finally, a third-generation inhibitor was shown to have good cellular activity and low toxicity. In addition to our findings, an alternative method of modeling time-dependent inhibition that simplifies assay setup and allows comparison of inhibition models is discussed.

  DOI：

  10.1021/acs.jmedchem.0c01006
• 作为产物：
  描述：

  5-溴戊酸 、 硫甲磺酸钠 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以80%的产率得到5-(Methylsulfonylthio)pentanoic acid
  参考文献：
  名称：

  枯草杆菌芽孢杆菌中单个氨基酸位点的多个负电荷的受控引入。

  摘要：

  在定点诱变和化学修饰相结合的策略中，使用甲硫基磺酸盐作为硫醇特异性修饰试剂，几乎可以创造出新的蛋白质表面环境。由于我们有兴趣将静电操作作为一种调节酶活性和特异性的手段，因此我们采用了这种方法来控制代表性丝氨酸蛋白酶枯草杆菌枯草芽孢杆菌（SBL）中单个位点的多个负电荷的掺入。合成了一系列的单，二和三酸性甲硫基磺酸盐，并用于修饰S2位点62，S1位点156和166，S1'位点217的SBL的半胱氨酸突变体。这些化学修饰的突变体（CMM）酶的动力学参数是在pH值为8的条件下确定的。在确保引入的非天然氨基酸侧链完全电离的条件下进行图6所示的操作。在SBL的S1，S1'和S2亚位中最多存在三个负电荷会导致活性降低多达11倍，这可能是由于干扰了催化水解反应过渡态的氧阴离子的稳定性。每单位负电荷的增加导致K（M）的增加和k（cat）的减少。但是，未观察到K（M）增加的上限，而k（cat）的减少达到极限值

  DOI：

  10.1016/s0968-0896(99)00167-4

文献信息

• Synthesis of new dithiolethione and methanethiosulfonate systems endowed with pharmaceutical interest
  作者：Elena Gabriele、Federica Porta、Giorgio Facchetti、Corinna Galli、Arianna Gelain、Fiorella Meneghetti、Isabella Rimoldi、Sergio Romeo、Stefania Villa、Chiara Ricci、Nicola Ferri、Akira Asai、Daniela Barlocco、Anna Sparatore

  DOI：10.3998/ark.5550190.p009.805

  日期：——

  Here we report synthetic methodology affording in the most efficient way the rapid preparation of new dithiolethiones (DTTs) and methanethiosulfonates (MTSs). These were evaluated as STAT3 inhibitors since these electrophilic systems could react with thiol groups of STAT3-SH2 domain. The results showed that MTSs strongly interacted with the SH2 domain, whereas the corresponding DTTs possessed lower

  在这里，我们报告了以最有效的方式快速制备新的二硫硫酮 (DTT) 和甲硫代磺酸盐 (MTS) 的合成方法。这些被评估为 STAT3 抑制剂，因为这些亲电子系统可以与 STAT3-SH2 结构域的硫醇基团反应。结果表明，MTSs 与 SH2 结构域强烈相互作用，而相应的 DTTs 具有较低的亲和力，与连接的杂环支架的性质无关。
• New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors
  作者：Elena Gabriele、Dario Brambilla、Chiara Ricci、Luca Regazzoni、Kyoko Taguchi、Nicola Ferri、Akira Asai、Anna Sparatore

  DOI：10.1080/14756366.2017.1350658

  日期：2017.1.1

  able to inhibit the NF-κB transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-κB inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents.

  合成了一组新的硫化药物混合物，主要源自咖啡酸、阿魏酸和迷迭香碱，并评估了它们抑制 STAT3 和 NF-κB 转录因子的能力。结果表明，大多数新的杂合化合物能够强烈且选择性地与 STAT3 结合，而母体药物在测试浓度下缺乏这种能力。其中一些还能够抑制HCT-116细胞系中的NF-κB转录活性，并在体外抑制HCT-116细胞增殖，IC50在微摩尔范围内，因此表明具有潜在的抗癌活性。总而言之，我们的研究描述了具有 STAT3/NF-κB 双重抑制活性的新衍生物的鉴定，这可能代表用于开发多靶点抗癌药物的热门化合物。
• Chemically modified enzymes with multiple charged variants
  申请人：GenenCor International, Inc.

  公开号：US20020127695A1

  公开（公告）日：2002-09-12

  This invention provides modified enzymes comprising one or more amino acid residues replaced by cysteine residues, where the cysteine residues are modified by replacing the thiol hydrogen in the cysteine residues with a substituent group providing a thiol side chain comprising a multiply charged moiety. The enzymes show improved interaction and/or specificity and/or activity with charged substrates.

  这项发明提供了一种改良酶，其中一个或多个氨基酸残基被半胱氨酸残基取代，半胱氨酸残基被替换为含有多重带电基团的硫醇侧链取代基，从而改良了酶与带电底物的相互作用和/或特异性和/或活性。
• MODIFIED CARBOHYDRATE PROCESSING ENZYME
  申请人：Davis Benjamin G.

  公开号：US20090181444A1

  公开（公告）日：2009-07-16

  A modified polypeptide having carbohydrate processing enzymatic activity is provided, said polypeptide comprising an amino acid sequence selected from: (a) the amino acid sequence of SEQ ID NO:2 comprising a mutation in at least one of W433, E432 and M439; (b) the amino acid sequence of an enzyme of glycosyl hydrolase family 1, comprising at least one mutation at an amino acid residue equivalent to W433, E432 or M439 of SEQ ID NO:2; and (c) a variant of (a) or (b) having carbohydrate processing enzymatic activity and comprising at least one amino acid mutation at a position equivalent to W433, E432 or M439 of SEQ ID NO:2.

  提供一种具有碳水化合物加工酶活性的改性多肽，该多肽包括以下氨基酸序列之一：(a) SEQ ID NO: 2的氨基酸序列，其中至少有一个W433、E432和M439突变；(b) 包括至少一个氨基酸残基等同于SEQ ID NO:2的W433、E432或M439的糖基水解酶家族1酶的氨基酸序列；以及(c) 具有碳水化合物加工酶活性的(a)或(b)的变体，其中包括至少一个氨基酸突变位于等同于SEQ ID NO:2的W433、E432或M439的位置。
• Enzyme-linked immunoassay, assay kits and pair-binding compounds
  申请人：THE UPJOHN COMPANY

  公开号：EP0117693A2

  公开（公告）日：1984-09-05

  An immunoassay, for measuring the amount of a ligand present in a medium, uses a luciferase-labelled binding pair member selected from a ligand and a receptor, in which the luciferase is linked to the binding pair member via its reactive sulfhydryl group and is thereby reversibly inactivated. A kit, for use in an immunoassay to determine the presence of a ligand in a medium, which comprises a plurality of containers, a first container containing luciferase-labelled receptor or ligand (a purified version of the ligand to be assayed) and a second container containing receptor which may be immobilised. New compounds have a reactive group which can react to cause reversible inactivation of luciferase and a group which can react with one or more sites on a binding receptor or ligand.

  一种用于测量培养基中配体存在量的免疫测定，使用荧光素酶标记的配对结合体，该结合体选自配体和受体，其中荧光素酶通过其活性巯基与配对结合体相连，从而可逆地失活。 用于免疫测定介质中配体存在的试剂盒，由多个容器组成，第一个容器装有荧光素酶标记的受体或配体（待测配体的纯化版本），第二个容器装有可固定的受体。 新化合物具有可导致荧光素酶可逆失活的反应基团，以及可与结合受体或配体上的一个或多个位点发生反应的基团。