H-Asp(OtBu)-D-Phe-Lys(Z)-Arg(Pbf)-Gly-OH | 1186382-57-9

• 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-Phe-Lys(Z)-Arg(Pbf)-Gly-OH
• CAS: 1186382-57-9
• 化学式: C₅₂H₇₃N₉O₁₃S
• 分子量: 1064.27
• InChiKey: OOLXJPXCSGHKKC-IJERZTCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  75.0
• 可旋转键数：
  26.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  335.63
• 氢给体数：
  10.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  H-Asp(OtBu)-D-Phe-Lys(Z)-Arg(Pbf)-Gly-OH 在 三异丙基硅烷 、 10% Pd/C 、 氢气 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 cyclo(Arg-Gly-Asp-D-Phe-Lys)-Biotin
  参考文献：
  名称：

  Chemical Functionalization of Bioceramics To Enhance Endothelial Cells Adhesion for Tissue Engineering

  摘要：

  To control the selective adhesion of human endothelial cells and human serum proteins to bioceramics of different compositions, a multifunctional ligand containing a cyclic arginine-glycine-aspartate (RGD) peptide, a tetraethylene glycol spacer, and a gallate moiety was designed, synthesized, and characterized. The binding of this ligand to alumina-based, hydroxyapatite-based, and calcium phosphate-based bioceramics was demonstrated. The conjugation of this ligand to the bioceramics induced a decrease in the nonselective and integrin-selective binding of human serum proteins, whereas the binding and adhesion of human endothelial cells was enhanced, dependent on the particular bioceramics.

  DOI：

  10.1021/jm301092r
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 H-Asp(OtBu)-D-Phe-Lys(Z)-Arg(Pbf)-Gly-OH
  参考文献：
  名称：

  Chemical Functionalization of Bioceramics To Enhance Endothelial Cells Adhesion for Tissue Engineering

  摘要：

  To control the selective adhesion of human endothelial cells and human serum proteins to bioceramics of different compositions, a multifunctional ligand containing a cyclic arginine-glycine-aspartate (RGD) peptide, a tetraethylene glycol spacer, and a gallate moiety was designed, synthesized, and characterized. The binding of this ligand to alumina-based, hydroxyapatite-based, and calcium phosphate-based bioceramics was demonstrated. The conjugation of this ligand to the bioceramics induced a decrease in the nonselective and integrin-selective binding of human serum proteins, whereas the binding and adhesion of human endothelial cells was enhanced, dependent on the particular bioceramics.

  DOI：

  10.1021/jm301092r

文献信息

• Comparing dendritic and self-assembly strategies to multivalency—RGD peptide–integrin interactions
  作者：Daniel J. Welsh、David K. Smith

  DOI：10.1039/c1ob05241a

  日期：——

  This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC50 of 125 μM (375 μM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 μM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.

  本文比较了组织配体阵列以结合整合素的共价和非共价方法。在共价策略中，线性 RGD 肽与第一代和第二代树枝状配体共轭，并使用荧光偏振竞争分析法证明第一代化合物能最有效地结合整合素，EC50 为 125 μM（每个肽单位为 375 μM）。因此，即使浓度高达 1 mM，这种树枝状化合物也比不与整合素结合的单价配体有效得多。不过，第二代化合物的效果明显较差，这表明在这种情况下，多价配体存在一个最佳配体密度。在多价性的非共价方法中，同样的 RGD 肽被疏水的 C12 链功能化，从而产生了一种经证明能够自组装的脂肽。这种脂肽在浓度为 200 ¼M 时就能与整合素有效结合。因此，这些结果表明，在实现配体阵列的多价组织方面，共价（树枝状）和非共价（胶束自组装）方法的效率相当。
• Efficient solid-phase synthesis of cyclic RGD peptides under controlled microwave heating
  作者：Keiichi Yamada、Izuru Nagashima、Masakazu Hachisu、Ichiro Matsuo、Hiroki Shimizu

  DOI：10.1016/j.tetlet.2011.12.069

  日期：2012.2

  Cyclic RGD peptides are potent antagonists for the αvβ3 integrin receptor. In this Letter, microwave-assisted solid-phase synthesis of cyclic RGD peptides is described. In a coupling reaction between Fmoc-Arg(Pbf)-OH and high-loading H-Gly-Trt(2-Cl) resin, multiple coupling reactions were required for completion under the conventional HBTU activation. We found that the use of COMU, a new coupling reagent

  环状RGD肽是用于α有效拮抗剂v β 3整联蛋白受体。在这封信中，描述了环状RGD肽的微波辅助固相合成。在Fmoc-Arg（Pbf）-OH与高负荷H-Gly-Trt（2-Cl）树脂之间的偶联反应中，在常规HBTU活化下需要多次偶联反应才能完成。我们发现，在微波加热至50°C的情况下，使用新型偶联剂COMU甚至可以加速树脂内部的反应。该方法适用于线性五肽H-Asp（OtBu）-Xxx-Yyy-Arg（Pbf）-Gly-OH（Xxx = d-Phe（p -Br）或d-Tyr，Yyy = Lys（ Boc）或MeVal）。将这些肽环化，然后脱保护，得到所需的具有高纯度的环状RGD肽。
• Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells
  作者：Eros Di Giorgio、Annalisa Ferino、Weizhe Huang、Sigrid Simonetti、Luigi Xodo、Rossella De Marco

  DOI：10.3389/fphar.2023.1237478

  日期：——

  The refractoriness of tumor cells to apoptosis represents the main mechanism of resistance to chemotherapy. Smac/DIABLO mimetics proved to be effective in overcoming cancer-acquired resistance to apoptosis as a consequence of overexpression of the anti-apoptotic proteins XIAP, cIAP1, and cIAP2. In this work, we describe a dual-targeting peptide capable of selectively activating apoptosis in cancer cells. The complex consists of a fluorescent periodic mesoporous organosilica nanoparticle that carries the short sequences of Smac/DIABLO bound to the αvβ3–integrin ligand. The dual-targeting peptide @PMO shows significantly higher toxicity in αvβ3-positive HeLa cells with respect to αvβ3-negative Ht29 cells. @PMO exhibited synergistic effects in combination with oxaliplatin in a panel of αvβ3-positive cancer cells, while its toxicity is overcome by XIAP overexpression or integrin β3 silencing. The successful uptake of the molecule by αvβ3-positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.

  肿瘤细胞对凋亡的耐受性是对化疗产生抗药性的主要机制。事实证明，Smac/DIABLO 拟效物能有效克服因抗凋亡蛋白 XIAP、cIAP1 和 cIAP2 过度表达而导致的癌症细胞对凋亡的耐药性。在这项研究中，我们描述了一种能够选择性激活癌细胞凋亡的双靶向肽。该复合物由荧光周期性介孔有机硅纳米粒子组成，该粒子携带与 αvβ3 整合素配体结合的 Smac/DIABLO 短序列。与αvβ3阴性的Ht29细胞相比，双靶向肽@PMO在αvβ3阳性的HeLa细胞中显示出明显更高的毒性。@PMO 与奥沙利铂联用时，在一组 αvβ3 阳性癌细胞中显示出协同效应，而 XIAP 过表达或整合素 β3 沉默可克服其毒性。αvβ3阳性细胞对该分子的成功吸收，使@PMO有望重新使许多癌症类型的细胞对凋亡敏感。