(+)-biotin tetrafluorophenyl ester | 173341-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: (+)-biotin tetrafluorophenyl ester
• 英文别名: Biotin-2,3,5,6-tetrafluorophenyl ester；(2,3,5,6-tetrafluorophenyl) 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate
• CAS: 173341-32-7
• 化学式: C₁₆H₁₆F₄N₂O₃S
• 分子量: 392.374
• InChiKey: FFPGMMMTGGBBLX-BHDSKKPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-biotin tetrafluorophenyl ester 在 碳酸氢钠 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 8.5h， 生成 di-tert-butyl 1,1'-(5-isocyanato-1,3-phenylene)(14S,14'S)-bis(1,12-dioxo-14-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)-5,8-dioxa-2,11-diazapentadecan-15-oate)
  参考文献：
  名称：

  Design and Synthesis of Bis-Biotin-Containing Reagents for Applications Utilizing Monoclonal Antibody-Based Pretargeting Systems with Streptavidin Mutants

  摘要：

  Previous studies have shown that pretargeting protocols, using cancer-targeting fusion proteins, composed of 4 anti-CD20 single chain Fv (scFv) fragments and streptavidin (scFv(4)-SAv), followed by a biotinylated dendrimeric N-acetyl-galactosamine blood clearing agent (CA), 1, then a radiolabeled DOTA-biotin derivative (a monobiotin), 3a, can provide effective therapy for lymphoma xenografts in mouse models. A shortcoming in this pretargeting system is that endogenous biotin may affect its efficacy in patients. To circumvent this potential problem, we investigated a pretargeting system that employs anti-CD20 scFv(4)-SAv mutant fusion proteins with radioiodinated bis-biotin derivatives. With that combination of reagents, good localization of the radiolabel to lymphoma tumor xenografts was obtained in the presence of endogenous biotin. However, the blood clearance reagents employed in the studies were ineffective, resulting in abnormally high levels of radioactivity in other tissues. Thus, in the present investigation a bis-biotin-trigalactose blood clearance reagent, 2, was designed, synthesized, and evaluated in vivo. Additionally, another DOTA-biotin derivative (a bis-biotin), 4a, was designed and synthesized, such that radiometals (e.g., In-111, Y-90, Lu-177) could be used in the pretargeting protocols employing scFv(4)-SAv mutant fusion proteins. Studies in mice demonstrated that the CA 2 was more effective than CA 1 at removing [I-125]scFv(4)-SAv-S45A mutant fusion proteins from blood. Another in vivo study compared tumor targeting and normal tissue concentrations of the new reagents (2 and [In-111]4b) with standard reagents (1 and [In-111]3b) used in pretargeting protocols. The study showed that lymphoma xenografts could be targeted in the presence of endogenous biotin when anti-CD20 fusion potent containing SAv mutants (scFv(4)-SAv-S45A or scFv(4)-SAv-Y43A) were employed in combination with CA 2 and [In-111]4b). Importantly, normal tissue concentrations of [In-111]4b were similar to those obtained using the standard reagents (1 and [In-111]3b), except that the blood and liver concentrations were slightly higher with the new reagents. While the reasons for the higher blood and liver concentrations are unknown, the differences in the galactose structures of the clearance agents 1 and 2 may play a role.

  DOI：

  10.1021/bc100030q
• 作为产物：
  描述：

  2,3,5,6-四氟苯酚 、 D-生物素 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到(+)-biotin tetrafluorophenyl ester
  参考文献：
  名称：

  新型生物素化 99mTc/Re-三羰基复合物的合成、表征和生物学评价

  摘要：

  报告了三种新的生物素化 fac-[(99m)Tc/Re(CO)3](+) 配合物与三齿配体 L1、L2 和 L3 的合成和生物学评价。L1-L3 含有螯合剂 2-((5-氨基戊基)(吡啶-2-基甲基)氨基)乙酸、2-(2-氨基乙硫基)-3-(1H-咪唑-4-基)丙酸和2 -amino-3-(1-carboxy-2-(1H-imidazol-4-yl)ethylthio)propanoic acid 分别通过胺基与生物素的羧酸盐结合。合成了 fac-[Re(CO)3(L1-L3)] 复合物，并通过 NMR 和 IR 表征，其中 ReL1 的 (N,N,O) 配位和 ReL2 的 (N,S,O) 配位和ReL3 得到确认。示踪复合物 fac-[(99m)Tc(CO)3(L1-L3)] 以高产率合成，并且在 24 小时内在 10(-3) M L-组氨酸和 L-半胱氨酸中高度稳定。此外，它们表现出高结合亲和力（>

  DOI：

  10.1002/jlcr.3372

文献信息

• Water soluble multi-biotin-containing compounds
  申请人：Wilbur Scott D.

  公开号：US20060228325A1

  公开（公告）日：2006-10-12

  Water-soluble discrete multi-biotin-containing compounds with at least three (3) biotin moieties are disclosed. The water-soluble biotin-containing compounds may additionally comprise one or more moieties that confer resistance to cleavage by biotinidase or that is cleavable in vitro or in vivo. The discrete multi-biotin-containing compounds may include a reactive moiety that provides a site for reaction with yet another moiety, such as a targeting, diagnostic or therapeutic functional moiety. Biotinylation reagents comprising water-soluble linker moieties are also disclosed and may additionally comprise a biotinidase protective group. Methods for amplifying the number of sites for binding biotin-binding proteins at a selected target using multi-biotin compounds also are disclosed.

  可溶于水的离散多生物素含有化合物，至少含有三个（3）生物素基团。这些可溶于水的生物素含有化合物可能还包括一个或多个使其对生物素酶的裂解具有抗性的基团，或者在体外或体内可被裂解的基团。这些离散的多生物素含有化合物可能包括一个反应性基团，提供与另一个基团（如靶向、诊断或治疗功能基团）反应的位点。还公开了包含可溶于水的连接基团的生物素化试剂，可能还包括生物素酶保护基团。还公开了使用多生物素化合物扩增在选定靶点上结合生物素结合蛋白的位点数量的方法。
• [EN] POLYBIOTIN COMPOUNDS FOR MAGNETIC RESONANCE IMAGINING AND DRUG DELIVERY<br/>[FR] COMPOSES DE POLYBIOTINE POUR IRM ET ADMINISTRATION DE MEDICAMENTS
  申请人：GEN HOSPITAL CORP

  公开号：WO2005032598A1

  公开（公告）日：2005-04-14

  The invention relates generally to biotin-containing compounds that are useful as imaging agents and drug-delivery agents. Another aspect of the invention relates to the aforementioned compounds chelated to a metal atom. In a preferred embodiment, the metal atom is a gadolinium. Another aspect of the invention relates to a compound comprising three biotin moieties and a pharmaceutical agent covalently bound to a heterocyclic core. In certain embodiments, the pharmaceutical agent is an antibiotic, antiviral, or radionuclide. Another aspect of the present invention relates to a method of treating disease involving administering the compounds of the invention to a mammal. Another aspect of the present invention relates to a method of acquiring a magnetic resonance image using the compounds of the invention.

  该发明涉及一般用作成像剂和药物传递剂的含生物素化合物。该发明的另一个方面涉及上述化合物螯合到金属原子上。在一个优选实施例中，金属原子是钆。该发明的另一个方面涉及一种包含三个生物素基团和一个与杂环核共价结合的药物剂的化合物。在某些实施例中，药物剂是抗生素、抗病毒药物或放射性核素。本发明的另一个方面涉及一种涉及向哺乳动物施用该发明化合物以治疗疾病的方法。本发明的另一个方面涉及使用该发明化合物获得磁共振图像的方法。
• The relationship between the structure of the headgroup of sphingolipids and their ability to form complex high axial ratio microstructures
  作者：Alex S Goldstein、Michael H Gelb、Paul Yager

  DOI：10.1016/s0009-3084(00)00204-8

  日期：2001.1

  examined for their ability to form complex high axial ratio microstructures (CHARMS), potential drug delivery vehicles. In general, if the modified ceramide had either a hydrogen bond donor or acceptor at C-1 and C-3, including hydrophobic or hydrophilic groups attached to C-1 microstructures formed. Tolerated groups include amides, esters, sulfonates, and ethers. If modification at C-3 added significant

  制备了具有化学修饰的极性头基的神经酰胺，并检查了其形成复杂的高轴向比微结构（CHARMS）（潜在的药物递送载体）的能力。通常，如果改性的神经酰胺在C-1和C-3处具有氢键供体或受体，包括与形成的C-1微结构相连的疏水或亲水基团。容许的基团包括酰胺，酯，磺酸盐和醚。如果C-3处的修饰增加了大量的体积（大于4个碳原子，而与亲水性无关），则会形成无定形聚集体。具有通过循环结构桥接的C-1和C-3的神经酰胺也可形成微结构。通过使用具有胺头基的鞘脂，可以在形成后共价修饰CHARM。
• One to chelate them all: investigation of a versatile, bifunctional chelator for 64Cu, 99mTc, Re and Co
  作者：Eszter Boros、Yi-Heng Scott Lin、Cara L. Ferreira、Brian O. Patrick、Urs O. Häfeli、Michael J. Adam、Chris Orvig

  DOI：10.1039/c0dt01458c

  日期：——

  We describe the synthesis of the dip (di-picolyl-carboxylate) bifunctional chelator system, capable of fast coordination of Cu2+, 64Cu2+ and Co2+, as well as the [M(CO)3]+-core (M = 99mTc, Re); it displays a variety of binding modes—tridentate when protected, tetradentate when deprotected. Syntheses of both the benzyl-nitro derivative and the benzyl-amino derivatives are described. The latter was coupled to biotin to show the viability of the system for functionalization with biomolecules. Besides coordination chemistry with stable isotopes, we also present labelling data with 64Cu and 99mTc, as well as in vitro stability studies.

  我们介绍了 dip（二巯基羧酸酯）双功能螯合剂系统的合成，该系统能够快速配位 Cu2+、64Cu2+ 和 Co2+，以及 [M(CO)3]+ 核（M = 99mTc，Re）；它显示出多种结合模式--受保护时为三叉型，去保护时为四叉型。本文介绍了苄基硝基衍生物和苄基氨基衍生物的合成过程。后者与生物素结合，显示了该系统与生物大分子功能化的可行性。除了稳定同位素的配位化学，我们还介绍了 64Cu 和 99mTc 的标记数据以及体外稳定性研究。
• Bio-functionalized Gold Nanoparticles for Surface-Plasmon- Absorption-Based Protein Detection
  作者：Wan-Joong Kim、Soo-Hee Choi、Young-S. Rho、Dong-Jin Yoo

  DOI：10.5012/bkcs.2011.32.12.4171

  日期：2011.12.20

  Bio-functionalized gold nanoparticles (AuNPs), which bio-specifically interact with biotin-(strept)avidin, were investigated in this study. AuNPs were functionalized with a synthetically-provided biotin-linked thiol (BLT), which was synthesized by amidation of the active ester of biotin with 2-mercaptoethylamine. The BLT-attached AuNP was bio-specific for streptavidin, making it potentially useful for biosensor applications. To test the bio-specific interactions, the colors, absorption spectra and TEM images were investigated for proteins such as streptavidin, cytochrome C, myoglobin and hemoglobin. The colors and absorption spectra changed when streptavidin was added to the BLT-attached AuNP solution. However, the color and spectra did not change when the other proteins were added to the same solution. These results show that the AuNPs provided a colloidal solution with excellent stability and highly selective absorption characteristics for streptavidin as a target molecule. Proteins were also screened in order to identify a general strategy for the use of optical biosensing proteins based on AuNPs. In addition, TEM images confirmed that streptavidin led the BLT-attached AuNPs to aggregate or precipitate.

  本研究探讨了生物功能化金纳米粒子（AuNPs），它能与生物素-（链）阿维丁（biotin-(strept)avidin）发生生物特异性相互作用。AuNPs 被合成提供的生物素连接硫醇（BLT）功能化，该硫醇是通过生物素的活性酯与 2-巯基乙胺酰胺化合成的。附着 BLT 的 AuNP 对链霉亲和素具有生物特异性，因此有可能用于生物传感器应用。为了测试生物特异性相互作用，研究了链霉亲和素、细胞色素 C、肌红蛋白和血红蛋白等蛋白质的颜色、吸收光谱和 TEM 图像。当链霉亲和素被添加到 BLT 附着的 AuNP 溶液中时，颜色和吸收光谱都发生了变化。然而，在同一溶液中加入其他蛋白质时，颜色和光谱没有变化。这些结果表明，AuNPs 提供的胶体溶液具有出色的稳定性和对链霉亲和素目标分子的高选择性吸收特性。为了确定使用基于 AuNPs 的光学生物传感蛋白质的一般策略，还对蛋白质进行了筛选。此外，TEM 图像证实链霉亲和素会导致 BLT 吸附的 AuNPs 聚合或沉淀。