Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• and Sjogren's disease are caused by activated macrophages [16]. Recently EC17, (λex = 465–490 nm and λem = 520–530 nm) a conjugate of folic acid and fluorescein isothiocyanate has been used for intraoperative surgery of ovarian cancer [17], lung adenocarcinoma [18][19][20], and breast cancer [21

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• -conjugated (FITC - fluorescein-isothiocyanate and PE - phycoerythrin) primary antibodies against IL-1β, IL-6, ICAM-1 PECAM-1, P-selectin, VE-cadherin (Beckman-Coulter). Endothelial cells were detached using trypsin (Sigma-Aldrich, USA) and washed in PBS. Cells were then incubated with the primary antibodies

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• in water (at pH 7.4) and of the protonated BODIPY dyes in 30% ACN in 0.1 M HCl. For both, fluorescein in 0.1 M NaOH was used as the reference (Φf = 0.89) [52]. These measurements revealed an increase in fluorescence by a factor of 7 to 50 upon protonation for the investigated BODIPYs, which is

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• , we employed fluorescein (Fl) as the reporter dye according to our previously published result [26]. Fl of high brightness is strongly encapsulated into the GC5A cavity (Ka = 5.0 × 106 M−1), accompanied with a drastic complexation-induced fluorescence quenching (Ifree/Ibound = 37). Taken together

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• fluorescein dyes to target mouse major satellite DNA using thermal denaturation, gel-shift electrophoresis, circular dichroism and fluorescence spectroscopy [89][90]. Some of these fluorescent probes were found to detect target sequences in mouse living cell lines and the nuclear substructures formed by

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• ]. The study was essentially performed with oligothymidylate models. First, the internalization of a 5’-fluorescein fma (Tps)14T in Vero, HeLa and GC-2 cells was poor but comparable to that of the control 5’-fluorescein (Tps)14T. These data can be explained by the decreased solubility in aqueous medium

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• probe and, therefore, the FRET is observed only when the labeled PNA probe, its complementary DNA and the CCP are present together (Figure 15B) [115][116]. It was demonstrated that the fluorescence signal obtained via FRET from CCP to fluorescein-labeled PNA was of an order of magnitude higher than the

• direct excitation of the fluorescein-labeled PNA [117]. Accordingly, the light harvesting properties of the oligomeric CCP improved the detection efficiency by signal amplification. Although the high specificity of PNA probes can already differentiate between complementary and mismatched DNA targets on

• polycationic dendritic fluorophore has also been used as a FRET donor to fluorescein-labeled pyrrolidinyl PNA probes giving a highly sequence-specific DNA detection at room temperature without requiring S1 digestion at a subnanomolar detection limit [124]. A new CCP called PFBT that can be excited at 488 nm

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• towards thiazolidines of type 30, the group of Clausen has proposed a base-catalyzed protocol using t-BuOH in water at 20 °C for a quite efficient cyclization between secondary N-propargylamines 28 and fluorescein isothiocyanate 29 (Scheme 7) [89]. More recently, Beauchemin and co-workers reported the

• 18 with 16. Synthesis of 5-(iodomethylene)-3-methylthiazolidines 27 described by Zhou. Mechanism that accounts for the formation of 27. Clausen’s synthesis of fluorescein thiazolidines 30. Synthesis of multiply substituted thiazolidines 33 from N-propargylamines 32 and blocked N-isothiocyanate

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• -yl)-4-methylmorpholinium chloride (DMTMMCl), a coupling reagent frequently used in peptide synthesis. Malanga et al. recently reported on the preparation of xanthene-dye-appended CDs with the most commonly used fluorescent probes rhodamine and fluorescein (Flu, 1). The conjugation of the 6-monoamino

• dyes were freshly synthesized starting from fluorescein (Flu, 1). Although the described synthetic procedures for the preparation of eosin dyes commonly use Br2, herein the less hazardous N-bromosuccinimide (NBS) was used as the source of bromine. Thus, eosin Y (2) was prepared in a single step from 1

• permanently immobilized on the silica gel column and only the targeted dibromofluorescein (3) was eluted. The structure of compound 3 was elucidated with the aid of 1D and 2D NMR experiments (Supporting Information File 1, Figures S10–S14). In the following step, dibrominated fluorescein 3 was nitrated using

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• indicated by a red rectangle), an adjacent overlapping poly(dA:dT) tract (MGB-binding site – by a blue rectangle). Fluo is a fluorescein label. A) Sequence derived from the murine pericentromere repeat fragment with only one target site for the polyamide F1-NH2 [2][3]. The target sequence is underlined. B

• ) and TINA-TFOs (shown in Figure 10) were 10 µM. Cu(I) was added as a mixture of components up to the final concentrations of CuSO4 and THPTA 5 mM and sodium ascorbate 10 mM. Non-denaturing gel electrophoresis analysis of conjugate 28 with fluorescein-labeled target HIV duplex (concentration 120 nM

• ), polyamide concentrations: 0, 0.45, 0.75, 1.13, 1.5, 2.25, 3, 0 μM (lines 1 to 8, respectively) in 0.05 M HEPES, 50 mM NaCl, 5 mM MgCl2, pH 7.2. Visualization of the gel was performed by monitoring fluorescence of the fluorescein-labeled duplex depicted in Figure 4. Supporting Information Synthesis and

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• inexpensive dyes, we prepared rhodamine- and fluorescein-appended cyclodextrins. The compounds were characterized by NMR and IR spectroscopy and MS spectrometry, their UV–vis spectra were recorded at various pH, and their purity was determined by capillary electrophoresis. Two potential models for the

• supramolecular assembly of the xanthene-dye-appended cyclodextrins were developed based on the set of data collected by the extensive NMR characterization. Keywords: DMT-MM; fluorescein; rhodamine; supramolecular assembly; Introduction Cyclodextrins (CDs) are cyclic oligosaccharides consisting of 6, 7 or 8

• representatives of this class are fluorescein and rhodamine (Figure 1), which have been applied as chemosensors [4] and have been widely exploited in various areas such as cell biology, microscopy, biotechnology, and ophthalmology due to their versatile photophysical properties. However, the chemical modification

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• these enantiomeric biosensors with orthogonal fluorophores (Figure 5). In our initial experiments, we utilized fluorescein (FAM) and cyanine 3 (Cy3), however, we observed that the difference in fluorophore structure resulted in an approximately two-fold difference in the equilibrium constants for the

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels

• Shintaro Kawano,
• Toshiyuki Kida,
• Mitsuru Akashi,
• Hirofumi Sato,
• Motohiro Shizuma and
• Daisuke Ono

Beilstein J. Org. Chem. 2015, 11, 2355–2364, doi:10.3762/bjoc.11.257

• method. The CD nanogel was labeled with fluorescein isothiocyanate (FITC) in the aqueous phase before emulsification. A Pickering emulsion was prepared by mixing the aqueous dispersion containing FITC labeled-CD nanogels (0.1 wt %) with n-dodecane (Φoil = 0.1) and subsequent shaking for 1 min. After

• to use. Anhydrous N,N-dimethylformamide (DMF) and 1,4-phenylene diisocyanate (PDI) were purchased from Wako Pure Chemical Industries, Ltd. (Japan). Toluene and n-dodecane were purchased from Kanto Chemical Co., Ltd. (Japan). Fluorescein-4-isothiocyanate was purchased from Dojin Chemical Co. Ltd

• homogenized for 1 min using a homogenizer (DIAX 900; Heidolph) at 8000 rpm (25 °C). The resulting emulsion was allowed to stand at 25 °C for 24 h. To confirm the adsorption of the CD nanogels at the oil–water interface in the emulsion, the CD nanogel (0.1 wt %) was labeled with fluorescein-4-isothiocyanate

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• ) and due to the presence of the –COOH group at the end of the side chain (in case of 5). Model 3: Oxygen radical absorbance capacity assay with fluorescein Figure 5 displays the kinetics of fluorescence decay for all studied monomers and dimers. The studied dimers exhibit activities that are similar or

• the fluorescence decay of fluorescein (13). In this model, there are competitive reactions of peroxide radicals between 13 and the studied compounds. The first attack in 13 is its phenolic group (see Scheme S4, Supporting Information File 1). As a monophenol without another substituents in the benzene

• ring, we expected 13 to be slightly less active than the studied ortho-methoxy substituted monomers and dimers. According to Huang et al. [32] if the condition 100 kFL[fluorescein] < kAm[monomer] (kAd[dimer]) is met, the rate of inhibited oxidation should be two orders of magnitude lower than the rate

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• and not sustainable. Similar to the redox properties of these organometallic complexes, some metal-free organic dyes such as Eosin Y, Rose Bengal, Fluorescein, and Methylene Blue, have shown superiority of their applications as photocatalysts, which are easy to handle, environmentally friendly

• 1), Rose Bengal gave a slightly lower yield (Table 1, entry 2), whereas Methylene Blue and Fluorescein gave poor yields (Table 1, entries 3 and 4). Under an O2 atmosphere, the yield of tetrahydroquinoline product 3a was decreased to 77% (Table 1, entry 5). When the molar proportion of 1a and 2a was

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• prepared either in well water-soluble form or as gels of high swelling. Two versatile synthetic strategies for introducing a fluorescent tag (rhodamine, fluorescein, nitrobenzofuran or coumarin) into the water-soluble epichlorohydrin branched cyclodextrin polymers were worked out and compared. The

• techniques and capillary electrophoresis. The applied synthetic routes were evaluated based on the molecular weight, cyclodextrin content of the products and the efficiency of labeling. Keywords: coumarin; fluorescein; functionalized monomers and polymers; nitrobenzofurazan; rhodamine; Introduction

• , we report the controlled, regioselective fluorescent labeling of neutral and cationic epichlorohydrin branched β-CD polymer with four different dyes (rhodamine, fluorescein, coumarin and nitrobenzofurazan). Our goal was the development of versatile synthetic strategies, yielding key intermediates of

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• thermal stability of the ILPR-DNA with respect to unfolding was also examined by emission spectroscopy in K+- and Na+-containing buffer, i.e., the melting temperature, Tm, of the dye-labelled quadruplex-forming ILPR sequence Fa2T [fluorescein-d(ACAG4TGTG4ACAG4TGTG4)-tetramethylrhodamine] was determined by

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• bromide was introduced as a part of a heterogenic two-chromophore system, to take advantage of very efficient FRET energy transfer process (77%) from fluorescein to the RNA-intercalated phenanthridinium fluorophore (Figure 8, left) [83]. The resulting fluorescent dye exhibited improved ds-RNA-marker

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• high water solubility was obtained and fully characterized both as for its chemical structure and for its capability to encapsulate substances. Fluorescein was used as probe molecule to test the complexation properties of the new material. Keywords: β-cyclodextrin; complexation; gelation

• hyper-branched β-CD polymer to form non-covalent adducts with organic molecules was tested by using sodium fluorescein (SF) as a probe molecule. The choice of this probe is due to previous use in the characterization of CD nanosponges [21] and to the presence of a strong chromofore for UV analysis. As a

• = β-CD/pyromellitic dianhydride molar ratio. NMR spectra of fluorescein in D2O solution (a) and in the presence of the hyper-branched β-CD polymer (b). pH range: 8.25–7.50. UV–vis spectrum of fluorescein with increasing amounts of hyper-branched β-CD polymer. pH range: 8.4–7.2. 1H NMR chemical shifts

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• a fluorescein-labeled model guest molecule which was successfully transported into the cells, thereby demonstrating the bimodal action of the derivative. The present work shows the versatility of CDs in smart applications and constitutes advancement to our previously shown PpIX-β-CD conjugation both

• suggestions as well as quantitation of subcellular processes (hydrolysis rate of 1, PpIX concentration) could only be confirmed with specific mechanistic biological studies, which lie outside the scope of the present work. We further incubated MCF7 cells with 2 pre-complexed with water-insoluble fluorescein

• ΄), 34.4 (C3), 27.1 (C2) ppm; MS (MALDI–TOF) m/z: 1685.2 (100%, [M + Νa]+), 1798.18 (89%, [M’ + Na]+); exact mass calculated for C66H119N9O39 ((1)2-CD = M): 1661.76 and for C71H126N10O41 ((1)3-CD = M’): 1774.808. Complexation of fluorescein isothiocyanate-labeled 1-adamantylamine with 2. The conjugate, 2

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• synthetic lectin HisHis is able to selectively bind to NANA immobilized on a substrate which serves as a model for a cell surface. To this end, we prepared a set of simple carbohydrate microarrays as well as fluorescein-isothiocyanate labeled HisHis (FITC-HisHis) and studied the selectivity and affinity of

• previously [39]. Fluorescein-labeled FITC-HisHis was obtained by labeling of Cys-His-Cys with fluorescein isothiocyanate, which was achieved by using an Fmoc-protected oligo(ethylene glycol) spacer synthesized in four steps from commercially available ethylenediamine (see Supporting Information File 1). The

• Wilhelms-Universität Münster). Milli-Q water was prepared from distilled water using a PureLab UHQ deionization system (Elga). Tetramethylrhodamine isothiocyanate-labeled concanavalin A (TRITC-ConA) was purchased from Sigma Aldrich. Fluorescein isothiocyanate-labeled peanut agglutinin (FITC-PNA) was

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• larger scales. However, the recent pursuit of environmentally more benign photoactive catalysts has focused on much cheaper metal-free dyes. Several commercially available fluorescein and xanthene dyes have been successfully applied to photoredox reactions, including radical substitutions at α-amino, β

• -carbonyl, and aryl moieties [9][10]. Among them, eosin Y, the 2’,4’,5’,7’-tetrabromo derivative of fluorescein, has been most widely employed. The redox potential of the EY+/EY* pair of 1.1 V (vs. SCE) is experimentally not available as both of the compounds are short-lived intermediates. However, the

End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition

• Ronald Okoth and
• Amit Basu

Beilstein J. Org. Chem. 2013, 9, 608–612, doi:10.3762/bjoc.9.66

• acid at the polymer terminus [6], a cis-alkene pentafluorophenol ester based terminating agent that introduces an amine-reactive capping agent [13], and cis-olefin terminating agents that directly introduce biotin and fluorescein at the polymer terminus [14]. A recent report describes the use of a cis

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• cycloadditions, the model compound fluoresceinyl azide 9[29][30] was first coupled to TPX derivatives 7a or 7b, under identical conditions as described for cRGD peptide 1b. The resulting polymers 8c and 8d were studied by determining the UV absorption peaks of fluorescein between 400 and 600 nm (Figure 4

• ). Absorption maxima of fluorescein were located at 457 nm and 481 nm, which can be ascribed to the presence of two isomeric forms (lacton versus carboxylate) of fluorescein [31]. These measurements clearly revealed the successful covalent functionalization of TPX with fluorescein by 1,3-dipolar cycloaddition

• . The copper-catalyzed method provided material 8c, which showed a small but significant absorption maximum for fluorescein at about 515 nm (dotted line versus dashed line) compared to starting TPX 7a. In contrast, the copper-free method led to intense fluorescein staining (polymer 8d, continuous line

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• of uncaging involves two completely distinct properties [80]. First, we must consider how well a molecule absorbs light, through the molar extinction coefficient, ε. This property measures how effectively a chromophore absorbs photons. Thus, fluorescein (ε = 80,000/M/cm) absorbs light much better