L-farnesyl cysteine

• 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: L-farnesyl cysteine
• 英文别名: S-farnesyl-L-cysteine；farnesyl-L-cysteine；S-Farnesyl cysteine；(2R)-2-amino-3-(3,7,11-trimethyldodeca-2,6,10-trienylsulfanyl)propanoic acid
• 化学式: C₁₈H₃₁NO₂S
• 分子量: 325.516
• InChiKey: SYSLNQMKLROGCL-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-farnesyl cysteine 、 苄磺酰氯 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.25h， 以38%的产率得到
  参考文献：
  名称：

  Probing the isoprenylcysteine carboxyl methyltransferase (Icmt) binding pocket: Sulfonamide modified farnesyl cysteine (SMFC) analogs as Icmt inhibitors

  摘要：

  Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the amide linkage of a hIcmt substrate can be replaced by a sulfonamide bond to achieve hIcmt inhibition. The most potent sulfonamide-modified farnesyl cysteine analog was 6ag with an IC(50) of 8.8 +/- 0.5 mu M for hIcmt. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.078
• 作为产物：
  描述：

  N-acetyl-S-farnesyl-L-cysteine 在 水 作用下， 以 aq. buffer 为溶剂， 反应 3.0h， 生成 L-farnesyl cysteine
  参考文献：
  名称：

  [EN] INHIBITION OF AMINOACYLASE 3 (AA3) IN THE TREATMENT OF CANCER
  [FR] INHIBITION DE L'AMINOACYLASE 3 (AA3) DANS LE TRAITEMENT DU CANCER

  摘要：

  目前的方法和组合物提供了治疗肝细胞癌（HCC）和其他类型癌症的治疗方法，包括胰腺癌和结肠癌等。因此，本公开的某些方面涉及使用本文所披露的一种或多种小分子抑制剂治疗HCC、胰腺癌和结肠癌的方法和组合物。在某些实施例中，小分子抑制剂是苯并噻唑、磺酰胺、噻唑烷酮或其他化学化合物。

  公开号：

  WO2019055825A1

文献信息

• Solid-Phase Synthesis of Lipidated Peptides
  作者：Maria Lumbierres、Jose M. Palomo、Goran Kragol、Sonja Roehrs、Oliver Müller、Herbert Waldmann

  DOI：10.1002/chem.200500476

  日期：2005.12.9

  methodology for the solid-phase synthesis of lipidated peptides has been developed. The approach is based on the use of previously synthesized building blocks and overcomes the limitations of previously reported methods, since long doubly lipidated peptides can be synthesized by using this route. Furthermore, it was thus possible to prepare a large number of N- and H-Ras peptides bearing a wide range

  已经开发了一种新的灵活高效的方法，用于脂化肽的固相合成。该方法基于先前合成的构件的使用，并克服了先前报道的方法的局限性，因为可以使用此途径合成长双脂化肽。此外，因此可以制备大量带有多种报道基团和/或连接基团的N-和H-Ras肽-研究生物学过程的有效工具。在效率和灵活性方面，这种固相方法优于溶液相合成。它可以在更短的时间内以百万毫克的量提供纯肽，并具有较高的总收率。
• Compounds for inhibition of protein methylation
  申请人：The President and Fellows of Harvard College

  公开号：US05202456A1

  公开（公告）日：1993-04-13

  The invention features a compound of the formula W-Y-Q-Z or W-Y-Z wherein W is a farnesyl group, a geranylgeranyl group, a substituted farnesyl group or a substituted geranylgeranyl group; ##STR1## wherein n=1, 2, 3, 4, 5, or 6; each of T.sub.1' . . . T.sub.n' and T.sub.1" . . . T.sub.n" is independently: Fl, Br, --NHCOCH.sub.3, --NH.sub.2, a peptide, an alkane group, an alkene group, an polyethyleneglycol group, a saturated fatty acid, an unsaturated fatty acid, a monosaccharide, or a disaccharide; and Z is --COOH or salts or esters thereof, --CONH.sub.2, --NO.sub.2, --PO.sub.3 or salts or esters thereof, --C N, or --SO.sub.3 or salts or esters thereof, provided that when W is farnesyl, Y is --S--, n=2, and either T.sub.2' or T.sub.2" is --NHCOCH.sub.3, then Z is not --COOH. The compounds of the invention are capable of interfering with enzymatic methylation of a peptide having the carboxyl-terminal motif --CAAX wherein C=cysteine, A=aliphatic amino acid, and X=any amino acid.

  该发明涉及一种化合物，其化学式为W-Y-Q-Z或W-Y-Z，其中W为顺式异戊烯基、长链异戊烯基、取代顺式异戊烯基或取代长链异戊烯基；Y为-（CH2）n-，其中n=1、2、3、4、5或6；T1'...Tn'和T1"...Tn"各自独立地为Fl、Br、-NHCOCH3、-NH2、肽、烷基、烯基、聚乙二醇基、饱和脂肪酸、不饱和脂肪酸、单糖或双糖；Z为-COOH或其盐或酯、-CONH2、-NO2、-PO3或其盐或酯、-CN或-SO3或其盐或酯，但当W为顺式异戊烯基时，Y为-S-，n=2，并且T2'或T2"为-NHCOCH3时，则Z不为-COOH。该发明的化合物能够干扰具有羧基末端基序列-CAAX（其中C=半胱氨酸，A=脂肪族氨基酸，X=任何氨基酸）的肽的酶促甲基化。
• Solid-phase synthesis of Biotin-S-Farnesyl-l-Cysteine, a surrogate substrate for isoprenylcysteine Carboxylmethyltransferase (ICMT)
  作者：Graeme I. Stevenson、Sarah Yong、Gregory A. Fechner、Juliette Neve、Aaron Lock、Vicky M. Avery

  DOI：10.1016/j.bmcl.2013.08.022

  日期：2013.10

  Inhibition of isoprenylcysteine Carboxylmethyltransferase (ICMT) is of particular interest as a potential target for the development of cancer chemotherapeutic agents. Screening for inhibitors of ICMT utilises a scintillation proximity assay (SPA) in which Biotin-S-Farnesyl-L-Cysteine (BFC) acts as a surrogate substrate. A solid-phase synthesis protocol for the preparation of BFC using 2-chlorotrityl chloride resin as a solid support has been developed to provide sufficient supply of BFC for high throughput screening (HTS) and subsequent chemistry campaigns to target inhibitors of ICMT. The BFC prepared by this method can be produced quickly on large scale and is stable when stored at -20 degrees C as a solid, in solution, or on the resin. (C) 2013 Elsevier Ltd. All rights reserved.
• Probing the isoprenylcysteine carboxyl methyltransferase (Icmt) binding pocket: Sulfonamide modified farnesyl cysteine (SMFC) analogs as Icmt inhibitors
  作者：Jaimeen D. Majmudar、Kalub Hahne、Christine A. Hrycyna、Richard A. Gibbs

  DOI：10.1016/j.bmcl.2011.01.078

  日期：2011.5

  Human isoprenylcysteine carboxyl methyltransferase (hIcmt) is a promising anticancer target as it is important for the post-translational modification of oncogenic Ras proteins. We herein report the synthesis and biochemical activity of 41 farnesyl-cysteine based analogs versus hIcmt. We have demonstrated that the amide linkage of a hIcmt substrate can be replaced by a sulfonamide bond to achieve hIcmt inhibition. The most potent sulfonamide-modified farnesyl cysteine analog was 6ag with an IC(50) of 8.8 +/- 0.5 mu M for hIcmt. (C) 2011 Elsevier Ltd. All rights reserved.
• [EN] INHIBITION OF AMINOACYLASE 3 (AA3) IN THE TREATMENT OF CANCER<br/>[FR] INHIBITION DE L'AMINOACYLASE 3 (AA3) DANS LE TRAITEMENT DU CANCER
  申请人：UNIV CALIFORNIA

  公开号：WO2019055825A1

  公开（公告）日：2019-03-21

  The current methods and compositions provide for therapeutic approaches to treating hepatocellular carcinoma (HCC) and other types of cancer including, for example, pancreatic and colon cancer. Accordingly, certain aspects of the disclosure relates to methods and compositions for treating HCC, pancreatic and colon cancer using one or more small molecule inhibitors disclosed herein. In certain embodiments, the small molecule inhibitor is a benzothiazine, a sulfonamide, a thiazolidinone or other chemical compound.

  目前的方法和组合物提供了治疗肝细胞癌（HCC）和其他类型癌症的治疗方法，包括胰腺癌和结肠癌等。因此，本公开的某些方面涉及使用本文所披露的一种或多种小分子抑制剂治疗HCC、胰腺癌和结肠癌的方法和组合物。在某些实施例中，小分子抑制剂是苯并噻唑、磺酰胺、噻唑烷酮或其他化学化合物。