H-Asp(OtBu)-D-Tyr(OtBu)-Lys(Boc)-Arg(Pbf)-Gly-OH | 1284294-23-0

• 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: H-Asp(OtBu)-D-Tyr(OtBu)-Lys(Boc)-Arg(Pbf)-Gly-OH
• CAS: 1284294-23-0
• 化学式: C₅₃H₈₃N₉O₁₄S
• 分子量: 1102.36
• InChiKey: DACPNLWEZGTPSC-BTSKBWHGSA-N

反应信息

• 作为反应物：
  描述：

  H-Asp(OtBu)-D-Tyr(OtBu)-Lys(Boc)-Arg(Pbf)-Gly-OH 在 N-羟基丁二酰亚胺 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 1,4-二巯基-2,3-丁二醇 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect

  摘要：

  The use of glioblastoma-targeted drug delivery system facilitates efficient delivery of chemotherapeutic agents to malignant gliomas in the central nervous system while minimizing high systemic doses associated with debilitating toxicities. To employ the high binding affinity of a cyclic RGD peptide (c(RGDyK), cyclic Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine) with integrin alpha(v)beta(3) over-expressed on tumor neovasculature and U87MG glioblastoma cells, we prepared paclitaxel-loaded c(RGDyK)-Poly(ethylene glycol)-block-poly(lactic acid) micelle (c(RGDyK)-PEG-PLA-PTX). In vitro physicochemical characterization of these novel micelles showed satisfactory encapsulated efficiency, loading capacity and size distribution. In vitro cytotoxicity studies proved that the presence of c(RGDyK) enhanced the anti-glioblastoma cell cytotoxic efficacy by 2.5 folds. The binding affinity of c(RGDyK)-PEG-PLA micelle with U87MG cells was also investigated. The competitive binding IC50 value of c(RGDyK)-PEG-PLA micelle was 26.30 nM, even lower than that of c(RGDyK) (56.23 nM). In U87MG glioblastoma-bearing nude mice model, biodistribution of I-125-radiolabeled c(RGDyK)-PEG-PLA or DiR encapsulated micelles and anti-glioblastoma pharmacological effect was investigated after intravenous administration. c(RGDyK)-PEG-PLA micelle accumulated in the subcutaneous and intracranial tumor tissue, and when loaded with PTX (c(RGDyK)-PEG-PLA-PTX), exhibited the strongest tumor growth inhibition among the studied paclitaxel formulations. The anti-glioblastoma effect of c(RGDyK)-PEG-PLA-PTX micelle was also reflected in the median survival time of mice bearing intracranial U87MG tumor xenografts where the median survival time of c(RGDyK)-PEG-PLA-PTX micelle-treated mice (48 days) was significantly longer than that of mice treated with PEG-PLA-FTX micelle (41.5 days), Taxol (R) (38.5 days) or saline (34 days). Therefore, our results suggested that c(RGDyK)-PEG-PLA micelle may be a potential drug delivery system in the treatment of integrin alpha(v)beta(3) over-expressed glioblastoma. (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jconrel.2009.12.020

文献信息

• Synthesis and evaluation of a deltic guanidinium analogue of a cyclic RGD peptide
  作者：Kenji Mishiro、Takahiro Ueno、Hiroshi Wakabayashi、Masato Fukui、Seigo Kinuya、Kazuma Ogawa

  DOI：10.1039/d3ob00089c

  日期：——

  A guanidine group is abundantly found in natural products and drugs. Guanidine has the highest basicity among many common functional groups in nature. Because of its high basicity, it generally exists as a protonated guanidinium and functions as a cationic hydrogen bond donor. Finding an appropriate bioisostere of guanidinium is challenging because of its high basicity and unique trigonal planar shape

  胍基大量存在于天然产物和药物中。胍在自然界许多常见的官能团中具有最高的碱度。由于其高碱性，一般以质子化的胍盐形式存在，起阳离子氢键供体的作用。由于其高碱度和独特的三角形平面形状，因此寻找合适的胍盐生物电子等排物具有挑战性。在这项研究中，我们使用环状精氨酸-甘氨酸-天冬氨酸 (RGD) 肽作为母体化合物，探索了“三角胍”作为胍盐生物电子等排物的可能性。我们合成了 c(deltic RGDyK)，其中 c(RGDyK) 中精氨酸残基的胍基被置换为 deltic 胍。目标结合分析，生物分布研究，和代谢稳定性测定是用 c(deltic RGDyK) 及其放射性碘化变体进行的。三角胍类似物肽表现出与母肽相似的生物学特性，并得到改进体内稳定性，表明三角胍可以作为胍盐的独特生物电子等排物。