N-[(9H-芴-9-基甲氧基)羰基]-3-({[({[(2-甲基-2-丙基)氧基]羰基}氨基)氧基]乙酰基}氨基)-L-丙氨酸 | 600153-12-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: N-[(9H-芴-9-基甲氧基)羰基]-3-({[({[(2-甲基-2-丙基)氧基]羰基}氨基)氧基]乙酰基}氨基)-L-丙氨酸
• 中文别名: 吡丙醚（蚊蝇磷）；NΑ-FMOC-NΒ-(N-BOC-氨基氧基乙酰基)-L-2,3-二氨基丙酸；Nα-Fmoc-Nβ-(N-Boc-氨基-氧基乙酰基)-L-2,3-二氨基丙酸
• 英文名称: Fmoc-DprAoa[Boc]-OH
• 英文别名: N-α-Fmoc-N-β-(N-tert-butyloxycarbonylaminooxyacetal)-L-diaminopropionic acid；Fmoc-L-Dap(Boc-Aoa)-OH；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]oxyacetyl]amino]propanoic acid
• CAS: 600153-12-6
• 化学式: C₂₅H₂₉N₃O₈
• 分子量: 499.521
• InChiKey: KHRQNEDYPNTPKW-FQEVSTJZSA-N

物化性质

• 密度：
  1.304±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  N-[(9H-芴-9-基甲氧基)羰基]-3-({[({[(2-甲基-2-丙基)氧基]羰基}氨基)氧基]乙酰基}氨基)-L-丙氨酸 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (S)-2-{3-[(2S,5S,11S,14R)-14-Benzyl-11-carboxymethyl-5-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-propionylamino}-3-{2-[1-(4-iodo-phenyl)-meth-(E)-ylideneaminooxy]-acetylamino}-propionic acid
  参考文献：
  名称：

  多聚环状RGD肽可作为靶向肿瘤的潜在工具：固相肽合成和化学选择性肟连接。

  摘要：

  alpha v beta 3整合素受体在人类转移和肿瘤诱导的血管生成中起重要作用。靶向该受体可以提供有关肿瘤的受体状态的信息，并可以进行特定的治疗计划。描述了多聚环（-RGDfE-）-肽的固相肽合成，由于多价效应，其提供了增强整联蛋白靶向性的可能性。这些肽含有一个氨基氧基，可进行通用的化学选择性肟连接。与对三甲基锡烷基苯甲醛结合产生放射性碘十二烷甲酰化的前体，这将使它们可用作靶向和成像表达αv beta 3的肿瘤细胞的潜在工具。不需要保护策略并且在温和条件下以高收率获得了缀合物。

  DOI：

  10.1002/chem.200204304

文献信息

• Near-infrared tunable bacteriochlorins equipped for bioorthogonal labeling
  作者：Jianbing Jiang、Masahiko Taniguchi、Jonathan S. Lindsey

  DOI：10.1039/c5nj00209e

  日期：——

  sciences. To broaden the scope for (bio)molecular labeling, nine lipophilic, wavelength-tunable (729–820 nm) bacteriochlorins (seven free base; two zinc chelates) have been prepared that bear a single bioconjugatable group. The latter include an aldehyde for oxime formation, a maleimido group for thioether formation, an ester or thioester group for traceless Staudinger ligation, or an azido group for click

  细菌氯霉素在近红外（NIR）光谱区域吸收很强，因此可能非常适合从能源科学到生命科学的光化学研究。为了扩大（生物）分子标记的范围，已制备了九个亲脂性，波长可调（729-820 nm）的细菌绿素（七个游离碱；两个锌螯合物），它们带有一个可生物结合的基团。后者包括用于肟形成的醛，用于硫醚形成的马来酰亚胺基，用于无痕施陶丁格连接的酯基或硫酯基，或用于点击化学的叠氮基。NIR波长调谐是通过在β-吡咯位置安装辅助色素，掺入环外6元酰亚胺部分或将游离碱大环化合物转化为螯合锌来实现的。使用三个合成的细菌氯霉素构件来构建细菌氯霉素组。在小分子以及两个四肽（每个含有一个非天然氨基酸残基）上确定了目标细菌绿素的生物结合能力。还建立了用于连续生物正交耦合的4×4矩阵。综上所述，这些研究满足了将NIR活性发色团用于各种光化学应用的两个关键分子设计标准（波长可调，可生物缀合）。
• A Chemically Cross-Linked Knottin Dimer Binds Integrins with Picomolar Affinity and Inhibits Tumor Cell Migration and Proliferation
  作者：Jun W. Kim、Frank V. Cochran、Jennifer R. Cochran

  DOI：10.1021/ja508416e

  日期：2015.1.14

  Molecules that target and inhibit alpha(v)beta(3), alpha(v)beta(5), and alpha(5)beta(1) integrins have generated great interest because of the role of these receptors in mediating angiogenesis and metastasis. Attempts to increase the binding affinity and hence the efficacy of integrin inhibitors by dimerization have been marginally effective. In the present work, we achieved this goal by using oxime-based chemical conjugation to synthesize dimers of integrin-binding cystine knot (knottin) miniproteins with low-picomolar binding affinity to tumor cells. A non-natural amino acid containing an aminooxy side chain was introduced at different locations within a knottin monomer and reacted with dialdehyde-containing cross-linkers of different lengths to create knottin dimers with varying molecular topologies. Dimers cross-linked through an aminooxy functional group located near the middle of the protein exhibited higher apparent binding affinity to integrin-expressing tumor cells compared with dimers cross-linked through an aminooxy group near the C-terminus. In contrast, the cross-linker length had no effect on the integrin binding affinity. A chemical-based dimerization strategy was critical, as knottin dimers created through genetic fusion to a bivalent antibody domain exhibited only modest improvement (less than 5-fold) in tumor cell binding relative to the knottin monomer. The best oxime-conjugated knottin dimer achieved an unprecedented 150-fold increase in apparent binding affinity over the knottin monomer. Also, this dimer bound 3650-fold stronger and inhibited tumor cell migration and proliferation compared with cilengitide, an integrin-targeting peptidomimetic that performed poorly in recent clinical trials, suggesting promise for further therapeutic development.
• Multimeric Cyclic RGD Peptides as Potential Tools for Tumor Targeting: Solid-Phase Peptide Synthesis and Chemoselective Oxime Ligation
  作者：Georgette Thumshirn、Ulrich Hersel、Simon L. Goodman、Horst Kessler

  DOI：10.1002/chem.200204304

  日期：2003.6.16

  angiogenesis. Targeting this receptor may provide information about the receptor status of the tumor and enable specific therapeutic planning. Solid-phase peptide synthesis of multimeric cyclo(-RGDfE-)-peptides is described, which offer the possibility of enhanced integrin targeting due to polyvalency effects. These peptides contain an aminooxy group for versatile chemoselective oxime ligation. Conjugation

  alpha v beta 3整合素受体在人类转移和肿瘤诱导的血管生成中起重要作用。靶向该受体可以提供有关肿瘤的受体状态的信息，并可以进行特定的治疗计划。描述了多聚环（-RGDfE-）-肽的固相肽合成，由于多价效应，其提供了增强整联蛋白靶向性的可能性。这些肽含有一个氨基氧基，可进行通用的化学选择性肟连接。与对三甲基锡烷基苯甲醛结合产生放射性碘十二烷甲酰化的前体，这将使它们可用作靶向和成像表达αv beta 3的肿瘤细胞的潜在工具。不需要保护策略并且在温和条件下以高收率获得了缀合物。