6-(N_α-tert-butoxycarbonyl-L-leucinoylamino)hexanoic acid | 391610-90-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 6-(N_α-tert-butoxycarbonyl-L-leucinoylamino)hexanoic acid
• 英文别名: 6-[[(2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]hexanoic acid
• CAS: 391610-90-5
• 化学式: C₁₇H₃₂N₂O₅
• 分子量: 344.451
• InChiKey: CIBJQAVHRGSUQL-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  24.0
• 可旋转键数：
  10.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  104.73
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6-(N_α-tert-butoxycarbonyl-L-leucinoylamino)hexanoic acid 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 6-((S)-2-Amino-4-methyl-pentanoylamino)-hexanoic acid (2-{2-[6-((S)-2-amino-4-methyl-pentanoylamino)-hexanoylamino]-ethyldisulfanyl}-ethyl)-amide; hydrochloride
  参考文献：
  名称：

  痕量水平的酶活性检测：直接筛选活性催化抗体的新视角

  摘要：

  在所支持的寡核苷酸的载体杂交之后，已经使用PCR方法检测到非常低水平的酶活性（10 -11 mol）。这种方法对于从组合文库中直接进行活性催化抗体筛选可能非常有用。

  DOI：

  10.1016/0040-4039(95)02122-1
• 作为产物：
  描述：

  6-氨基己酸 在 sodium hydroxide 、 氯化亚砜 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.67h， 生成 6-(N_α-tert-butoxycarbonyl-L-leucinoylamino)hexanoic acid
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Thapsigargin Analogues for Targeting Apoptosis to Prostatic Cancer Cells

  摘要：

  A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+](i)) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with w-amino acids [HOOC-(CH2)(n),NH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L-serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.

  DOI：

  10.1021/jm010985a

文献信息

• Model studies on the utility of nucleophiles bound to insoluble supports for enzymatic peptide synthesis
  作者：Andreas Könnecke、Sabine Dettlaff、Hans-Dieter Jakubke

  DOI：10.1007/bf00799560

  日期：1982.3
• Design, Synthesis, and Pharmacological Evaluation of Thapsigargin Analogues for Targeting Apoptosis to Prostatic Cancer Cells
  作者：Carsten M. Jakobsen、Samuel R. Denmeade、John T. Isaacs、Alyssa Gady、Carl E. Olsen、Søren Brøgger Christensen

  DOI：10.1021/jm010985a

  日期：2001.12.1

  A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+](i)) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with w-amino acids [HOOC-(CH2)(n),NH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L-serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.
• Detection of enzyme activity at trace levels: A new perspective for the direct screening of active catalytic antibodies
  作者：T.D. Hua、V. Rolland-Fulcrand、R. Lazaro、P. Viallefont、M-P. Lefranc、M. Weill

  DOI：10.1016/0040-4039(95)02122-1

  日期：1996.1

  activity (10−11 mol) has been detected using a PCR method following a vector hybridisation of a supported oligonucleotide. This methodology could be very useful for direct active catalytic antibody screening from a combinatorial library.

  在所支持的寡核苷酸的载体杂交之后，已经使用PCR方法检测到非常低水平的酶活性（10 -11 mol）。这种方法对于从组合文库中直接进行活性催化抗体筛选可能非常有用。