fluorescein isothiocyanate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: fluorescein isothiocyanate
• 英文别名: 2-(3,6-Dihydroxy-9h-xanthen-9-yl)-5-isothiocyanatobenzoic acid；2-(3,6-dihydroxy-9H-xanthen-9-yl)-5-isothiocyanatobenzoic acid
• 化学式: C₂₁H₁₃NO₅S
• 分子量: 391.404
• InChiKey: BGOKZTMWUXWSSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  fluorescein isothiocyanate 、 DL-赖氨酸-叔丁氧羰基 在 potassium carbonate buffer 作用下， 以 丙酮 、 盐酸 、 溶剂黄146 为溶剂， 反应 14.0h， 生成 N_ε-FITC-lysine
  参考文献：
  名称：

  Homing of negatively charged albumins to the lymphatic system

  摘要：

  The present study shows the lymphatic distribution of the negatively charged anti-HIV-l agents succinylated or aconytilated human serum albumins (HSAs) in rats. Quantitation of blood and lymphatic concentrations of these proteins was performed through fluorescence detection of the fluorescein isothiocyanate (FITC)-labeled proteins. At several time points after i.v. injection, samples were taken from the cannulated thoracic duct and the carotid artery. Distribution of the negatively charged albumins (NCAs) to lymph was much more rapid than that of albumin itself and was dependent on the total net negative charge added to the protein: the half-life times of lymphatic equilibration were 15, 30, and 120 min for FITC-labeled aconytilated HSA, FITC-labeled succinylated HSA, and FITC-labeled HSA, respectively. Lymph to blood concentration ratios of the studied compounds obtained at steady state approached unity. In addition, the fluorescence in both body fluids was shown to represent unchanged labeled proteins. It was therefore inferred that the NCAs efficiently passed the endothelial barrier from blood to the interstitial compartment. Subsequently, we studied whether a specialized process was involved in the endothelial passage of the NCAs to the lymph. The following observations supported such a mechanism: a) preinjection of the scavenger receptor blockers polyinosinic- and formaldehyde treated HSA reduced the transport from blood to the lymphatic compartment of FITC-labeled aconytilated HSA by more than 90%; b) the rate of lymphatic distribution was largely reduced when the body temperature of the rat was lowered to 28 degrees; and c) pre-administration of chloroquine resulted in a significant reduction in the lymphatic distribution of the NCAs. These data collectively indicate that a scavenger receptor-mediated process is involved in the transendothelial transport of NCAs. In situ localization in lymph nodes of the rat showed that FITC -labeled aconytilated and succinyrated HSA are mainly present in the germinal center and parafollicular zones. The efficient distribution of these anionized proteins to the lymphatic system is of particular interest for HIV therapy, taking into account that replication of HIV mainly takes place in the lymphoid system. The observation that macromolecules, through charge modification, can extravasate through a receptor-mediated transcytotic process is potentially of major importance for the delivery of drugs with macromolecular carriers to cells not directly in contact with the blood. (C) 1999 Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(99)00224-5

文献信息

• On-site reaction for PPARγ modification using a specific bifunctional ligand
  作者：Hiroyuki Kojima、Toshimasa Itoh、Keiko Yamamoto

  DOI：10.1016/j.bmc.2017.10.024

  日期：2017.12

  demonstrate this strategy by using fluorescein as a probe and peroxisome proliferator activated receptor γ (PPARγ) as a target protein. The reactions were evaluated by ESI-mass analysis and the binding site and modes of binding were revealed by X-ray crystallization analysis. The proposed methodology can easily convert a covalent ligand into chemical tool for protein functional analysis and the identification

  位点特异性标记是阐明靶蛋白生物学功能的重要方法。在这里，我们报告了一种针对特定地点进行化学标记的策略，称为“现场反应”。我们设计并易于合成具有两个反应位点，一个烯酮和一个叠氮部分的双功能配体。该策略涉及与蛋白质的现场共轭加成反应，然后进行Hüisgen环加成反应。我们通过使用荧光素作为探针和过氧化物酶体增殖物激活的受体γ证明了这一策略（PPARγ）作为靶蛋白。通过ESI质量分析评估反应，并通过X射线结晶分析揭示结合位点和结合方式。所提出的方法可以轻松地将共价配体转化为用于蛋白质功能分析和药物靶标鉴定的化学工具。
• Reversible Lysine Modification on Proteins by Using Functionalized Boronic Acids
  作者：Pedro M. S. D. Cal、Raquel F. M. Frade、Carlos Cordeiro、Pedro M. P. Gois

  DOI：10.1002/chem.201500127

  日期：2015.5.26

  install azide and alkyne bioorthogonal functions on proteins, which may then be further reacted with their bioorthogonal counterparts. These constructs were also used to add polyethylene glycol (PEG) to insulin, a modification which has been shown to be reversible in the presence of fructose. Finally, iminoboronates were used to assemble a folic acid/paclitaxel small‐molecule/drug conjugate in situ with

  氨基硼酸酯已被用于在蛋白质上成功安装叠氮化物和炔烃的生物正交功能，然后可以使其与它们的生物正交对应物进一步反应。这些构建体还用于向胰岛素中添加聚乙二醇（PEG），这种修饰已被​​证明在果糖存在下是可逆的。最后，亚氨基硼酸酯用于原位组装叶酸/紫杉醇小分子/药物结合物，对NCI-H460癌细胞的IC 50 值为20.7 n M，对CRL-1502非癌细胞的细胞毒性可忽略不计。
• Synthesis, Characterization, and Remarkable Biological Properties of Cyclodextrins Bearing Guanidinoalkylamino and Aminoalkylamino Groups on Their Primary Side
  作者：Nikolaos Mourtzis、Maria Paravatou、Irene M. Mavridis、Michael L. Roberts、Konstantina Yannakopoulou

  DOI：10.1002/chem.200701650

  日期：2008.5.9

  guanidinoethylamino-beta-CD. The title CDs are rigid, cyclic alpha-D-glucopyranose oligomers (heptamers or octamers) with branches that resemble lysine and arginine side chains that enable multiple interactions with suitable substrates. Thus, they bear similarities to known cell-penetrating peptides. Indeed, the compounds were found to cross the membranes of HeLa cells and penetrate inside the cytoplasm

  在β-和γ-环糊精（CD）的伯侧引入氨基烷基氨基和胍基烷基氨基取代基，产生了一系列新颖的化合物，这些化合物已通过NMR光谱学和质谱学进行了广泛表征。β-和γ-CD伯侧的溴化，并与纯亚烷基二胺在7 atm的压力下反应，得到氨基烷基氨基衍生物，然后将其在伯氨基上进行鸟苷化，得到相应的胍基烷基氨基-CD。这些化合物是水溶性的，并显示pK（a）值，使它们在中性pH值下大多能质子化。例如，对于氨基乙基氨基-β-CD，pK（a（1））约为6.4，pK（a（2））约为9.5，对于pK（a（1））约为7.8，对于pK（a（2））约为11.0。胍基乙基氨基-β-CD。标题CD是刚性的，环状α-D-吡喃葡萄糖低聚物（七聚体或八聚体），其分支类似于赖氨酸和精氨酸侧链，能够与合适的底物进行多次相互作用。因此，它们与已知的穿透细胞的肽具有相似性。确实，已发现这些化合物穿过HeLa细胞膜并迅速渗透到细胞质内部，在15
• First-in-Class Dual Hybrid Carbonic Anhydrase Inhibitors and Transient Receptor Potential Vanilloid 1 Agonists Revert Oxaliplatin-Induced Neuropathy
  作者：Andrea Angeli、Laura Micheli、Fabrizio Carta、Marta Ferraroni、Tracey Pirali、Asia Fernandez Carvajal、Antonio Ferrer Montiel、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.2c01911

  日期：2023.1.26
• RAAV WITH CHEMICALLY MODIFIED CAPSID
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：US20210205467A1

  公开（公告）日：2021-07-08

  The invention is directed to the field of gene therapy, i.e. gene delivery into target cells, tissue, organ and organism, and more particularly to gene delivery via viral vectors. The inventors showed that it is possible by chemical coupling to modulate the coupling of a ligand in the surface of the capsid of AAV, for example AAV2 and AAV3b. In particular, the present invention relates to a recombinant Adeno-Associated Virus (rAAV) vector particle having at least one primary amino group contained in the capsid proteins, chemically coupled with at least one ligand L, wherein coupling of said ligand L is implemented through a bond comprising a —CSNH— bond and an optionally substituted aromatic moiety. Particularly, the inventors tested the chemical coupling of mannose ligand on AAV2 for subretinally injection to rats. The present invention further relates to a method for chemically coupling an Adeno-Associated Virus (AAV) vector particle with at least one ligand L and to a Recombinant Adeno-Associated Virus (rAAV) vector particle obtained by said method as well as a pharmaceutical composition comprising it and their corresponding medical use.