Trt-Gly-Gly-Phe-Gly-OBn | 173723-56-3

• 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: Trt-Gly-Gly-Phe-Gly-OBn
• 英文别名: Trt-Gly-Gly-Phe-Gly-OBzl；benzyl 2-[[(2S)-3-phenyl-2-[[2-[[2-(tritylamino)acetyl]amino]acetyl]amino]propanoyl]amino]acetate
• CAS: 173723-56-3
• 化学式: C₄₁H₄₀N₄O₅
• 分子量: 668.792
• InChiKey: ZKSLBJDQUPOBMG-BHVANESWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Trt-Gly-Gly-Phe-Gly-OBn 在 palladium on activated charcoal 1,4-环己二烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以98%的产率得到Trt-Gly-Gly-Phe-Gly-OH
  参考文献：
  名称：

  Synthesis of Carboxymethylpullulan-Peptide-Doxorubicin Conjugates and Their Properties.

  摘要：

  发现多柔比星（DXR）的氨基与羧甲基支链淀粉（CMPul）的羧基直接或通过包括甘-甘-苯丙-甘、甘-苯丙-甘-甘和甘-甘-甘-甘的四肽间隔物结合。这些偶联物的DXR含量为6.1-7.1%，羧甲基的取代度为每个糖单元0.6。这些偶联物在磷酸盐缓冲盐水（PBS，pH 7.4）中聚集，形成内部为疏水性DXR、外部为亲水性CMPul的胶束。通过高效液相色谱法测定了在大鼠肝脏溶酶体酶存在下，从这些偶联物中释放的DXR的量。药物释放速率因偶联物的不同而异。通过甘-甘-苯丙-甘连接的CMPul-DXR偶联物在24小时内释放了其35%的DXR。另一方面，没有间隔物的CMPul-DXR偶联物未释放出自由DXR。通过监测单次静脉注射后肿瘤重量，研究了每种偶联物对携带Walker 256肿瘤的大鼠的抗肿瘤效果。与DXR相比，通过甘-甘-苯丙-甘和甘-苯丙-甘-甘间隔物连接的CMPul-DXR偶联物显著抑制了肿瘤生长，而通过甘-甘-甘-甘连接的CMPul-DXR偶联物的抗肿瘤效果低于DXR。即使剂量相当于20 mg/kg的DXR，没有间隔物的CMPul-DXR偶联物也没有显示出体内抗肿瘤效果。

  DOI：

  10.1248/cpb.43.1931
• 作为产物：
  描述：

  Trt-Gly-Gly-OH 、 Phe-Gly-OBn p-toluenesulfonate 在 N-甲基吗啉 、 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 Trt-Gly-Gly-Phe-Gly-OBn
  参考文献：
  名称：

  Synthesis of Carboxymethylpullulan-Peptide-Doxorubicin Conjugates and Their Properties.

  摘要：

  发现多柔比星（DXR）的氨基与羧甲基支链淀粉（CMPul）的羧基直接或通过包括甘-甘-苯丙-甘、甘-苯丙-甘-甘和甘-甘-甘-甘的四肽间隔物结合。这些偶联物的DXR含量为6.1-7.1%，羧甲基的取代度为每个糖单元0.6。这些偶联物在磷酸盐缓冲盐水（PBS，pH 7.4）中聚集，形成内部为疏水性DXR、外部为亲水性CMPul的胶束。通过高效液相色谱法测定了在大鼠肝脏溶酶体酶存在下，从这些偶联物中释放的DXR的量。药物释放速率因偶联物的不同而异。通过甘-甘-苯丙-甘连接的CMPul-DXR偶联物在24小时内释放了其35%的DXR。另一方面，没有间隔物的CMPul-DXR偶联物未释放出自由DXR。通过监测单次静脉注射后肿瘤重量，研究了每种偶联物对携带Walker 256肿瘤的大鼠的抗肿瘤效果。与DXR相比，通过甘-甘-苯丙-甘和甘-苯丙-甘-甘间隔物连接的CMPul-DXR偶联物显著抑制了肿瘤生长，而通过甘-甘-甘-甘连接的CMPul-DXR偶联物的抗肿瘤效果低于DXR。即使剂量相当于20 mg/kg的DXR，没有间隔物的CMPul-DXR偶联物也没有显示出体内抗肿瘤效果。

  DOI：

  10.1248/cpb.43.1931

文献信息

• Drug complex
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US20030171262A1

  公开（公告）日：2003-09-11

  A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C 1-4 )alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

  一种药物复合物，其特征在于将药物化合物（如抗肿瘤剂）的残留物和通过在使得多元醇化反应基本完全的条件下处理葡聚糖而获得的羧基（C1-4）烷基葡聚糖多元醇，通过含有氨基酸的间隔物或者由肽键连接的2至8个氨基酸组成的间隔物相互结合。该复合物的特点在于具有卓越的对肿瘤部位的选择性，从而表现出高度的抗肿瘤活性，并且能够实现毒性的减少。
• Body fluid compatible and biocompatible resin
  申请人：Sugawara Shuichi

  公开号：US20050113560A1

  公开（公告）日：2005-05-26

  A body fluid compatible and biocompatible resin for use in a medical treatment involving a contact of said resin with at least one member selected from the group consisting of a body fluid and a biological tissue, which comprises at least one substituted oxyalkylene polymer having a weight average molecular weight of from 1,000 to 1,000,000 and represented by the following formula (1): wherein each of R 1 , R 2 and R 3 independently represents a hydrogen atom or a —CH 2 R 4 group, and each R 4 independently represents a hydroxyl group or a —OR 5 group (wherein R 5 represents a group selected from the group consisting of a C 1 -C 10 aliphatic hydrocarbyl group, a C 6 -C 10 aryl group, a —R 6 COOH group and a derivative thereof, and a —CH 2 —O—CH 2 —CH(OH)—CH 2 —OR 7 group, wherein R 6 represents a C 1 -C 10 aliphatic hydrocarbylene group and R 7 represents a C 1 -C 10 aliphatic hydrocarbyl group or a C 6 -C 10 aryl group), provided that all of R 1 , R 2 , and R 3 are not simultaneously hydrogen atoms; and 10≦x≦10,000 and 0≦y≦10,000.

  一种与体液兼容且生物相容的树脂，用于医疗治疗中与体液或生物组织中的至少一种成员接触，其包括至少一种代替的氧烷基聚合物，其重量平均分子量为1,000至1,000,000，由以下公式（1）表示： 其中，R1、R2和R3分别独立表示氢原子或—CH2R4基团，每个R4独立表示羟基或—OR5基团（其中R5表示从C1-C10脂肪族羟基烃基、C6-C10芳烃基、—R6COOH基团及其衍生物和—CH2—O—CH2—CH（OH）—CH2—OR7基团中选择的基团，其中R6表示C1-C10脂肪族羟基烃基，R7表示C1-C10脂肪族羟基烃基或C6-C10芳烃基），前提是R1、R2和R3不同时为氢原子；且10≦x≦10,000，0≦y≦10,000。
• Drug complexes
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06436912B1

  公开（公告）日：2002-08-20

  A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C1-4)alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized-in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

  一种药物复合物，其特征在于将药物化合物（如抗肿瘤药物）的残留物和通过在能够实现基本完全多元醇化的条件下处理葡聚糖而获得的羧基（C1-4）烷基葡聚糖多元醇通过含有氨基酸的间隔物或含有肽键的2至8个氨基酸的间隔物相互结合。该复合物的特征在于具有优异的肿瘤位点选择性，从而表现出高抗肿瘤活性，并实现毒性的降低。
• Synthesis of Carboxymethylpullulan-Peptide-Doxorubicin Conjugates and Their Properties.
  作者：Hideo NOGUSA、Toshiro YANO、Satoshi OKUNO、Hiroshi HAMANA、Kazuhiro INOUE

  DOI：10.1248/cpb.43.1931

  日期：——

  The amino group of doxorubicin (DXR) was found to be bound to the carboxyl group of carboxymethylpullulan (CMPul) either directly or through tetrapeptide spacers, including Gly-Gly-Phe-Gly, Gly-Phe-Gly-Gly and Gly-Gly-Gly-Gly. These conjugates had DXR contents of 6.1-7.1%, with the degree of substitution of carboxymethyl groups being 0.6 per sugar moiety. These conjugates associate in phosphate-buffered saline (PBS)(pH 7.4), forming micelles with hydrophobic DXR inside and hydrophilic CMPul on the outside. The amounts of DXR released from the conjugates in the presence of rat liver lysosomal enzymes were determined by HPLC. The rate of the drug release differed among the conjugates tested. CMPul-DXR conjugate bound through Gly-Gly-Phe-Gly released 35% of its DXR over 24 h. On the other hand, CMPul-DXR conjugate without spacer released no free DXR. The antitumor effect of each conjugate in rats bearing Walker 256 was studied by monitoring the tumor weights after a single intravenous injection. Compared with DXR, CMPul-DXR conjugates bound through Gly-Gly-Phe-Gly and Gly-Phe-Gly-Gly spacers significantly suppressed the tumor growth, while CMPul-DXR conjugate bound through Gly-Gly-Gly-Gly showed less antitumor effect than DXR. CMPul-DXR conjugate without spacer showed no in vivo antitumor effect even at a dose equivalent to as much as 20 mg/kg of DXR.

  发现多柔比星（DXR）的氨基与羧甲基支链淀粉（CMPul）的羧基直接或通过包括甘-甘-苯丙-甘、甘-苯丙-甘-甘和甘-甘-甘-甘的四肽间隔物结合。这些偶联物的DXR含量为6.1-7.1%，羧甲基的取代度为每个糖单元0.6。这些偶联物在磷酸盐缓冲盐水（PBS，pH 7.4）中聚集，形成内部为疏水性DXR、外部为亲水性CMPul的胶束。通过高效液相色谱法测定了在大鼠肝脏溶酶体酶存在下，从这些偶联物中释放的DXR的量。药物释放速率因偶联物的不同而异。通过甘-甘-苯丙-甘连接的CMPul-DXR偶联物在24小时内释放了其35%的DXR。另一方面，没有间隔物的CMPul-DXR偶联物未释放出自由DXR。通过监测单次静脉注射后肿瘤重量，研究了每种偶联物对携带Walker 256肿瘤的大鼠的抗肿瘤效果。与DXR相比，通过甘-甘-苯丙-甘和甘-苯丙-甘-甘间隔物连接的CMPul-DXR偶联物显著抑制了肿瘤生长，而通过甘-甘-甘-甘连接的CMPul-DXR偶联物的抗肿瘤效果低于DXR。即使剂量相当于20 mg/kg的DXR，没有间隔物的CMPul-DXR偶联物也没有显示出体内抗肿瘤效果。