[(2S,5S,8S,11S)-8-[4-(2-Aminooxy-acetylamino)-butyl]-5-benzyl-11-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid | 858124-61-5

• 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: [(2S,5S,8S,11S)-8-[4-(2-Aminooxy-acetylamino)-butyl]-5-benzyl-11-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid
• 英文别名: 2-[(2S,5S,8S,11S)-8-[4-[(2-aminooxyacetyl)amino]butyl]-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
• CAS: 858124-61-5
• 化学式: C₂₉H₄₄N₁₀O₉
• 分子量: 676.73
• InChiKey: BGNRHAPZAZUPHO-TUFLPTIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  312
• 氢给体数：
  10
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  、 [(2S,5S,8S,11S)-8-[4-(2-Aminooxy-acetylamino)-butyl]-5-benzyl-11-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid 在 ammonium acetate buffer 作用下， 以41%的产率得到
  参考文献：
  名称：

  New Solid Support for the Synthesis of 3‘-Oligonucleotide Conjugates through Glyoxylic Oxime Bond Formation

  摘要：

  A novel solid support 1 was synthesized to incorporate glyoxylic aldehyde functionality at the oligonucleotide 3'-terminus. 6-mer and 11-mer oligonucleotide sequences containing 3'-glyoxylic aldehyde functionality were prepared by using this support. These modified oligonucleotides were coupled to reporters containing an aminooxy group to prepare oligonucleotide 3'-conjugates through glyoxylic oxime bond formation. The hydrolytic stability of a glyoxylic oxime linkage was also investigated.

  DOI：

  10.1021/ol062607b
• 作为产物：
  描述：

  cyclo(-Asp(OtBu)-Phe-Lys-Arg(Pmc)Gly-) 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 [(2S,5S,8S,11S)-8-[4-(2-Aminooxy-acetylamino)-butyl]-5-benzyl-11-(3-guanidino-propyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid
  参考文献：
  名称：

  肽-寡核苷酸缀合物的高效合成：化学选择性肟和噻唑烷的形成。

  摘要：

  提出了一种融合策略，用于合成肽-寡核苷酸共轭物（POC）。通过肟和噻唑烷的形成来实现肽与寡核苷酸的化学选择性连接。通过用含醛的寡核苷酸处理含氧胺的肽进行肟偶联，反之亦然。通过将用半胱氨酸残基酰化的肽偶联至通过醛官能团衍生的寡核苷酸，实现噻唑烷形成的连接。对于这两种方法，不需要保护策略并且在温和的水性条件下以高收率获得缀合物。此外，肟连接被证明可用于直接缀合双链寡核苷酸。结合分子生物学工具，

  DOI：

  10.1002/1521-3765(20010917)7:18<3976::aid-chem3976>3.0.co;2-x

文献信息

• Efficient bioconjugation of 5-fluoro-5-deoxy-ribose (FDR) to RGD peptides for positron emission tomography (PET) imaging of αvβ3 integrin receptor
  作者：Sergio Dall'Angelo、Qingzhi Zhang、Ian N. Fleming、Monica Piras、Lutz F. Schweiger、David O'Hagan、Matteo Zanda

  DOI：10.1039/c3ob40550h

  日期：——

  The utility of 5-fluoro-5-deoxyribose (FDR) as an efficient bioconjugation agent for radiolabelling of the RGD peptides c(RGDfK) and c(RGDfC) is demonstrated. The bioconjugation is significantly superior to that achieved with 2-fluoro-2-deoxyglucose (FDG) and benefits from the location of the fluorine at C-5, and that ribose is a 5-membered ring sugar rather than a 6-membered ring. Both features favour ring opening to the aldehydic form of the sugar to promote smooth oxime ligation with aminooxy ether functionalised peptides. [18F]FDR was prepared in this study by synthesis from fluoride-18 using an automated synthesis protocol adapting that used routinely for [18F]FDG. c(RGDfK) was functionalised with an aminooxyacetyl group (Aoa) via its lysine terminus, while c(RGDfC) was functionalised with an aminooxyhexylmaleimide (Ahm) through a cysteine–maleimide conjugation. Bioconjugation of [18F]FDR to c(RGDfC)-Ahm proved to be more efficient than c(RGDfK)-Aoa (92% versus 65%). The unlabelled (19F) bioconjugates c(RGDfK)-Aoa-FDR and c(RGDfC)-Ahm-FDR were prepared and their in vitro affinity to purified integrin αvβ3 was determined. c(RGDfK)-Aoa-FDR showed the greater affinity. Purified “hot” bioconjugates c(RGDfK)-Aoa-[18F]FDR and c(RGDfC)-Ahm-[18F]FDR were assayed by incubation with MCF7, LNCaP and PC3 cell lines. In both cases the conjugated RGD peptides showed selectivity for PC3 cells, which express αvβ3 integrin, with the c(RGDfK)-Aoa-[18F]FDR demonstrating better binding, consistent with its higher in vitro affinity. The study demonstrates that [18F]FDR is an efficient bioconjugation ligand for RGD bioactive peptides.

  研究表明，5-氟-5-脱氧核糖（FDR）作为RGD肽c(RGDfK)和c(RGDfC)的放射标记高效生物偶联剂具有实用性。与2-氟-2-脱氧葡萄糖（FDG）相比，生物偶联效果显著优越，这得益于氟原子位于C-5位置，以及核糖是五元环糖而非六元环糖的特点。这两个特性有利于糖环开环形成醛式，促进与氨基氧乙基功能化肽的顺利肟连接。在本研究中，[18F]FDR通过从氟-18开始，采用适应常规[18F]FDG合成方法的自动化合成协议制备。c(RGDfK)通过其赖氨酸末端与氨基氧乙酰基（Aoa）功能化，而c(RGDfC)通过半胱氨酸-马来酰亚胺连接与氨基氧己基马来酰亚胺（Ahm）功能化。[18F]FDR与c(RGDfC)-Ahm的生物偶联证明比c(RGDfK)-Aoa更高效（92%对65%）。制备了未标记的（19F）生物偶联物c(RGDfK)-Aoa-FDR和c(RGDfC)-Ahm-FDR，并测定了它们对纯化整合素αvβ3的体外亲和力。c(RGDfK)-Aoa-FDR显示出更高的亲和力。纯化的“热”生物偶联物c(RGDfK)-Aoa-[18F]FDR和c(RGDfC)-Ahm-[18F]FDR通过与MCF7、LNCaP和PC3细胞系共孵育进行检测。两种情况下，结合的RGD肽均显示出对表达αvβ3整合素的PC3细胞的选择性，其中c(RGDfK)-Aoa-[18F]FDR显示出更好的结合效果，与其更高的体外亲和力一致。该研究表明，[18F]FDR是RGD生物活性肽的高效生物偶联配体。
• Highly Efficient Synthesis of Peptide-Oligonucleotide Conjugates: Chemoselective Oxime and Thiazolidine Formation
  作者：Damien Forget、Didier Boturyn、Eric Defrancq、Jean Lhomme、Pascal Dumy

  DOI：10.1002/1521-3765(20010917)7:18<3976::aid-chem3976>3.0.co;2-x

  日期：2001.9.17

  A convergent strategy for the synthesis of peptide-oligonucleotide conjugates (POC) is presented. Chemoselective ligation of peptide to oligonucleotide was accomplished by oxime and thiazolidine formation. Oxime conjugation was performed by treating an oxyamine-containing peptide with an aldehyde-containing oligonucleotide or vice versa. Ligation by thiazolidine formation was achieved by coupling a

  提出了一种融合策略，用于合成肽-寡核苷酸共轭物（POC）。通过肟和噻唑烷的形成来实现肽与寡核苷酸的化学选择性连接。通过用含醛的寡核苷酸处理含氧胺的肽进行肟偶联，反之亦然。通过将用半胱氨酸残基酰化的肽偶联至通过醛官能团衍生的寡核苷酸，实现噻唑烷形成的连接。对于这两种方法，不需要保护策略并且在温和的水性条件下以高收率获得缀合物。此外，肟连接被证明可用于直接缀合双链寡核苷酸。结合分子生物学工具，
• New Solid Support for the Synthesis of 3‘-Oligonucleotide Conjugates through Glyoxylic Oxime Bond Formation
  作者：Nicolas Spinelli、Om Prakash Edupuganti、Eric Defrancq、Pascal Dumy

  DOI：10.1021/ol062607b

  日期：2007.1.1

  A novel solid support 1 was synthesized to incorporate glyoxylic aldehyde functionality at the oligonucleotide 3'-terminus. 6-mer and 11-mer oligonucleotide sequences containing 3'-glyoxylic aldehyde functionality were prepared by using this support. These modified oligonucleotides were coupled to reporters containing an aminooxy group to prepare oligonucleotide 3'-conjugates through glyoxylic oxime bond formation. The hydrolytic stability of a glyoxylic oxime linkage was also investigated.