Nα-(4-pentynoyl)-Nδ-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)lysine | 1280211-97-3

• 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: Nα-(4-pentynoyl)-Nδ-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)lysine
• 英文别名: (2S)-6-[[2-[[(2S)-2-[[(2S)-2-[[2-[[4-(benzenecarbonothioylsulfanyl)-4-cyanopentanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-2-(pent-4-ynoylamino)hexanoic acid
• CAS: 1280211-97-3
• 化学式: C₄₃H₅₅N₇O₈S₂
• 分子量: 862.084
• InChiKey: HYVLXFWIEKDXSU-GDXQJKBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  60
• 可旋转键数：
  27
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  293
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  炔丙基脲 、 Fmoc-甘氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-苯丙氨酸 、 Dde-Lys(Fmoc)-OH 、 4-氰基-4-(硫代苯甲酰)戊酸 在 N,N-二异丙基乙胺 、 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以61%的产率得到Nα-(4-pentynoyl)-Nδ-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)lysine
  参考文献：
  名称：

  Synthesis of biodegradable multiblock copolymers by click coupling of RAFT-generated heterotelechelic polyHPMA conjugates

  摘要：

  A new strategy for the synthesis of biodegradable high molecular weight N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymeric carriers has been designed. An enzyme-sensitive, alkyne-functionalized, chain transfer agent (CTA-GFLG-alkyne; N-alpha-(4-pentynoyl)-N-delta-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)-lysine) was synthesized and used to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization and copolymerization of HPMA. Post-polymerization modification with 4,4'-azobis(azidopropyl 4-cyanopentanoate) resulted in the formation of heterotelechelic HPMA copolymers containing terminal alkyne and azide groups. Chain extension via click reaction resulted in high molecular weight multiblock copolymers. Upon exposure to papain, these copolymers degraded into the initial blocks. Similar results were obtained for copolymers of HPMA with N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione and N-methacryloyl-glycylphenylalanylleucylglycyl-gemcitabine. The new synthetic method presented permits the synthesis of biocompatible, biodegradable high molecular weight HPMA copolymer-anticancer drug conjugates that possess long-circulation times and augmented accumulation in solid tumor tissue due to the enhanced permeability and retention effect. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.reactfunctpolym.2010.10.005

文献信息

• Synthesis of biodegradable multiblock copolymers by click coupling of RAFT-generated heterotelechelic polyHPMA conjugates
  作者：Jiyuan Yang、Kui Luo、Huaizhong Pan、Pavla Kopečková、Jindřich Kopeček

  DOI：10.1016/j.reactfunctpolym.2010.10.005

  日期：2011.3

  A new strategy for the synthesis of biodegradable high molecular weight N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymeric carriers has been designed. An enzyme-sensitive, alkyne-functionalized, chain transfer agent (CTA-GFLG-alkyne; N-alpha-(4-pentynoyl)-N-delta-(4-cyano-4-(phenylcarbonothioylthio)pentanoyl-glycylphenylalanylleucylglycyl)-lysine) was synthesized and used to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization and copolymerization of HPMA. Post-polymerization modification with 4,4'-azobis(azidopropyl 4-cyanopentanoate) resulted in the formation of heterotelechelic HPMA copolymers containing terminal alkyne and azide groups. Chain extension via click reaction resulted in high molecular weight multiblock copolymers. Upon exposure to papain, these copolymers degraded into the initial blocks. Similar results were obtained for copolymers of HPMA with N-methacryloylglycylphenylalanylleucylglycyl thiazolidine-2-thione and N-methacryloyl-glycylphenylalanylleucylglycyl-gemcitabine. The new synthetic method presented permits the synthesis of biocompatible, biodegradable high molecular weight HPMA copolymer-anticancer drug conjugates that possess long-circulation times and augmented accumulation in solid tumor tissue due to the enhanced permeability and retention effect. (C) 2010 Elsevier Ltd. All rights reserved.