- Cyanine dye conjugates as probes for live cell imaging
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A series of fluorescent compounds suitable for live cell imaging is described. Functionalized forms of four different asymmetric cyanine dyes are reported that are amenable to peptide conjugation. The photophysical properties of the modified dyes and conj
- Carreon, Jay R.,Stewart, Kelly M.,Mahon Jr., Kerry P.,Shin, Stephanie,Kelley, Shana O.
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- Thiazole Orange-Peptide Conjugates: Sensitivity of DNA Binding to Chemical Structure
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(Equation presented) Derivatives of the highly fluorescent and DNA-binding dye thiazole orange (TO) are described that feature appended peptides. Functionalization of TO can be achieved at either of the endocyclic nitrogens, and the photophysical properties and DNA-binding modes are sensitive to the position of the tethered peptide. A series of TO-peptide conjugates are described, demonstrating the utility of a solid-phase synthesis approach to their preparation and illustrating how the photophysical and DNA-binding properties of the compounds are influenced by chemical structure.
- Carreon, Jay R.,Mahon Jr., Kerry P.,Kelley, Shana O.
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- New cyanine-oligonucleotide conjugates: Relationships between chemical structures and properties
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Because the influence of the chemical structure of monomethine cyanine-oligo-2′-deoxyribonudeotide (ODN) conjugates on their binding and fluorescence properties has remained largely undetermined, we synthesized and studied a wide range of conjugates with various structural patterns. Different cyanine dyes such as thiocyanine, quinocyanine, and thiazole orange isomers were obtained. In the case of unsymmetrical cyanines. the linker was attached to either the quinoline or the benzothiazole nucleus. The influence of the ODN counterpart was evaluated by linking the cyanines to the 5'-end or to an internucleotidic phosphate. In the first case, the influence of neighboring nucleic bases was studied, whereas in the second, the stereochemical configuration at the phosphorus atom bearing the cyanine was investigated. We report here on relationships between the structures of the dyes and conjugates and some of their properties, such as the stability and fluorescence changes observed on their hybridization with the target sequence. This study provides useful information towards the design of ODN-cyanine conjugates.
- Lartia, Remy,Asseline, Ulysse
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- A small-sized benzothiazole-indolium fluorescent probe: The study of interaction specificity targeting c-MYC promoter G-quadruplex structures and live cell imaging
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A small-sized c-MYC promoter G-quadruplex selective fluorescent BZT-Indolium binding ligand was demonstrated for the first time as a highly target-specific and photostable probe for in vitro staining and live cell imaging and it was found to be able to inhibit the amplification of the c-MYC G-rich sequence (G-quadruplex) and down-regulate oncogene c-MYC expression in human cancer cells (HeLa). This journal is
- Zheng, Bo-Xin,She, Meng-Ting,Long, Wei,Xu, Yong-Yu,Zhang, Yi-Han,Huang, Xuan-He,Liu, Wenjie,Hou, Jin-Qiang,Wong, Wing-Leung,Lu, Yu-Jing
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- Synthesis, spectral properties of rhodanine complex merocyanine dyes as well as their effect on K562 leukemia cells
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Two rhodanine complex merocyanine dyes 9a and 9b were synthesized and their structures were confirmed by 1H NMR, IR, MS, HRMS and UV-Vis spectra. From the spectral properties of the two dyes, it could be found that the λmax of the dyes showed hypsochromic shifts with the increase of permittivity in protonic solvents, and bathochromic shifts with the increase of refractive index in non protonic solvents. The interactions of two dyes with DNA or BSA were also studied under physiological conditions. The results showed that the quantum yield of DNA-dye 9a was up to 29.5 times compared with free dye 9a. Dyes 9a and 9b were researched in Photodynamic Therapy (PDT) as well. It was demonstrated that supplementation of dye 9a or 9b as photosensitizers for PDT in K562 cells decreases the survival rate.
- Xiang, Jun-Feng,Liu, Yan-Xia,Sun, Dan,Zhang, Su-Juan,Fu, Yi-Le,Zhang, Xiang-Han,Wang, Lan-Ying
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- Design of thiazole orange oligonucleotide probes for detection of DNA and RNA by fluorescence and duplex melting
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We have synthesised a range of thiazole orange (TO) functionalised oligonucleotides for nucleic acid detection in which TO is attached to the nucleobase or sugar of thymidine. The properties of duplexes between TO-probes and their DNA and RNA targets strongly depend on the length of the linker between TO and the oligonucleotide, the position of attachment of TO to the nucleotide (major or minor groove) and the mode of attachment of thiazole orange (via benzothiazole or quinoline moiety). This information can be used to design probes for detection of target nucleic acids by fluorescence or duplex melting. With cellular imaging in mind we show that 2′-OMe RNA probes with TO at the 5-position of uracil or the 2′-position of the ribose sugar are particularly effective, exhibiting up to 44-fold fluorescence enhancement against DNA and RNA, and high duplex stability. Excellent mismatch discrimination is achieved when the mispaired base is located adjacent to the TO-modified nucleotide rather than opposite to it. The simple design, ease of synthesis and favourable properties of these TO probes suggest applications in fluorescent imaging of DNA and RNA in a cellular context.
- Klimkowski, Piotr,De Ornellas, Sara,Singleton, Daniel,El-Sagheer, Afaf H.,Brown, Tom
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- Twisted cyanines: A non-planar fluorogenic dye with superior photostability and its use in a protein-based fluoromodule
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The cyanine dye thiazole orange (TO) is a well-known fluorogenic stain for DNA and RNA, but this property precludes its use as an intracellular fluorescent probe for non-nucleic acid biomolecules. Further, as is the case with many cyanines, the dye suffer
- Shank, Nathaniel I.,Pham, Ha H.,Waggoner, Alan S.,Armitage, Bruce A.
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- Fluorescence Detection of KRAS2 mRNA Hybridization in Lung Cancer Cells with PNA-Peptides Containing an Internal Thiazole Orange
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We previously developed reporter-peptide nucleic acid (PNA)-peptides for sequence-specific radioimaging and fluorescence imaging of particular mRNAs in cells and tumors. However, a direct test for PNA-peptide hybridization with RNA in the cytoplasm would be desirable. Thiazole orange (TO) dye at the 5′ end of a hybridization agent shows a strong increase in fluorescence quantum yield when stacked upon a 5′ terminal base pair, in solution and in cells. We hypothesized that hybridization agents with an internal TO could distinguish a single base mutation in RNA. Thus, we designed KRAS2 PNA-IGF1 tetrapeptide agents with an internal TO adjacent to the middle base of the 12th codon, a frequent site of cancer-initiating mutations. Our molecular dynamics calculations predicted a disordered bulge with weaker hybridization resulting from a single RNA mismatch. We observed that single-stranded PNA-IGF1 tetrapeptide agents with an internal TO showed low fluorescence, but fluorescence escalated 5-6-fold upon hybridization with KRAS2 RNA. Circular dichroism melting curves showed ~10 °C higher Tm for fully complementary vs single base mismatch TO-PNA-peptide agent duplexes with KRAS2 RNA. Fluorescence measurements of treated human lung cancer cells similarly showed elevated cytoplasmic fluorescence intensity with fully complementary vs single base mismatch agents. Sequence-specific elevation of internal TO fluorescence is consistent with our hypothesis of detecting cytoplasmic PNA-peptide:RNA hybridization if a mutant agent encounters the corresponding mutant mRNA. (Figure Presented).
- Sonar, Mahesh V.,Wampole, Matthew E.,Jin, Yuan-Yuan,Chen, Chang-Po,Thakur, Mathew L.,Wickstrom, Eric
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- Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine
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Proteome profiling by activated esters identified >9000 ligandable lysines but they are limited as covalent inhibitors due to poor hydrolytic stability. Here we report our efforts to design and discover a new series of tunable amine-reactive electrophiles (TAREs) for selective and robust labeling of lysine. The major challenges in developing selective probes for lysine are the high nucleophilicity of cysteines and poor hydrolytic stability. Our work circumvents these challenges by a unique design of the TAREs that form stable adducts with lysine and on reaction with cysteine generate another reactive electrophiles for lysine. We highlight that TAREs exhibit substantially high hydrolytic stability as compared to the activated esters and are non-cytotoxic thus have the potential to act as covalent ligands. We applied these alternative TAREs for the intracellular labeling of proteins in different cell lines, and for the selective identification of lysines in the human proteome on a global scale.
- Backus, Keriann M.,Boatner, Lisa M.,Cao, Jian,Farhi, Jonathan,Houk, Kendall N.,Li, Linwei,Raj, Monika,Spangle, Jennifer,Tang, Kuei-Chien
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- Monitoring and Modulating mtDNA G-Quadruplex Dynamics Reveal Its Close Relationship to Cell Glycolysis
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The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, incl
- Chen, Shuo-Bin,Chen, Xiu-Cai,Dai, Jing,Huang, Zhi-Shu,Luo, Wen-Hua,Shao, Wen,Tan, Jia-Heng,Tang, Gui-Xue,Zeng, Shu-Tang
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supporting information
p. 20779 - 20791
(2021/12/14)
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- Synthesis and antileishmanial evaluation of thiazole orange analogs
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Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC50 12–42 nM), while ring disjunction analogs were both less potent and less toxic. Changes in DNA melting temperature were modest when synthetic oligonucleotides were incubated with selected analogs (ΔTm ≤ 5 °C), with ring disjunction analogs showing the least effect on this parameter. Despite the high antileishmanial potency of the target compounds, their toxicity and relatively flat SAR suggests that further information regarding the target(s) of these molecules is needed to aid their development as antileishmanials.
- Abdelhameed, Ahmed,Liao, Xiaoping,McElroy, Craig A.,Joice, April C.,Rakotondraibe, Liva,Li, Junan,Slebodnick, Carla,Guo, Pu,Wilson, W. David,Werbovetz, Karl A.
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supporting information
(2019/11/28)
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- Benzoindole derivative for G-quadruplex RNA fluorescent probe and preparation method and application of benzoindole derivative
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The invention belongs to the technical field of G-quadruplex RNA detection, and discloses a benzoindole derivative for a G-quadruplex RNA fluorescent probe and a preparation method and application ofthe benzoindole derivative. The molecular structure of the benzoindole derivative is shown as a formula (I); in the formula, R is selected from hydroxyl, acylamino, carboxyl or phosphate, n is the number of carbon atoms, and n is equal to 1-6. The benzoindole derivative disclosed by the invention can be used as a fluorescent probe to dye G-quadruplex RNA in cells, the detection process is not interfered by other components, the benzoindole derivative has the characteristics of high fluorescence intensity and strong anti-interference capability, and the G-quadruplex RNA can be specifically recognized in vitro and vivo; meanwhile, the benzoindole derivative is simple in preparation process, low in cost, stable in structure and convenient to store, and has a wide application prospect in the G-quadruplex RNA biological function research.
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Paragraph 0041-0043
(2020/12/10)
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- saisai zuo orange derivative and its preparation method and as a double-helical nucleic acid fluorescent molecular probe application
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The invention belongs to the field of a medical technology and relates to a thiazol orange derivative, its manufacturing method and an application of the thiazol orange derivative used as a double helix nucleic acid fluorescence molecular probe. On the precondition of not changing a parent structure of thiazol orange (TO), different substituent groups are introduced into quinoline ring atom to prepare a series of derived structures. The general structural formula is as defined in the specification, wherein X: O and S; Y: halogen; R1: hydrogen, C1-C4 alkyl group and dimethylamino C1-C4 alkyl group; and R2: hydrogen, C1-C4 alkyl group, amino group, C1-C4 alkylamine and di(C1-C4 alkyl)amido. Results show that binding ability of modified molecules and double-helix DNA is raised and fluorescent response sensitivity is also enhanced.
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Paragraph 0015; 0050; 0051; 0052; 0053
(2017/08/25)
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- Design, synthesis and biological evaluation of novel unsymmetrical azines as quorum sensing inhibitors
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Targeting quorum sensing signals using quorum sensing inhibitors has opened new avenues for the application of known antibiotics. In this context, twenty five unsymmetrical azines were synthesised and evaluated as quorum sensing inhibitors. An efficient one-pot procedure was adopted that directly links 3-methyl-2-(methylthio)benzo[d]thiazol-3-ium salt, hydrazine hydrate and substituted aldehyde to give the designed compounds. The synthesized compounds were preliminarily tested for their potential to inhibit CviR receptor based QS signals in Chromobacterium violaceum. The bioassay screening results suggested that two compounds exhibited potent QS inhibition activity against CviR receptor, showing violacein inhibition (>50%) at 200 μM. Further, the putative positive hits were checked for their potential to inhibit LasR receptor-based QS using the PlasB-gfp(ASV) biomonitor strain of Pseudomonas aeruginosa. These compounds were found to inhibit the QS-mediated GFP signals in a dose dependant manner. Two active compounds also exhibited biofilm clearance at 50 μM concentration. Docking studies were performed to examine their potential to bind to the LasR protein of Pseudomonas aeruginosa.
- Chourasiya, Sumit S.,Kathuria, Deepika,Singh, Shaminder,Sonawane, Vijay C.,Chakraborti, Asit K.,Bharatam, Prasad V.
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p. 80027 - 80038
(2015/10/05)
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- Coherent quenching of a fluorophore for the design of a highly sensitive in-stem molecular beacon
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(Figure Presented) Excitonic interaction was utilized to design a highly sensitive in-stem molecular beacon (ISMB) in which both a fluorophore and a quencher on D-threoninols are incorporated as a pseudo base pair (see scheme; optimized combination with Cy3 and modified Methyl Red). Minimization of the difference between λmax of the fluorophore and quencher maximized quenching efficiency.
- Hara, Yuichi,Fujii, Taiga,Kashida, Hiromu,Sekiguchi, Koji,Liang, Xingguo,Niwa, Kosuke,Takase, Tomokazu,Yoshida, Yasuko,Asanuma, Hiroyuki
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supporting information; experimental part
p. 5502 - 5506
(2010/10/02)
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- Photosensitized DNA cleavage promoted by amino acids
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A novel class of DNA cleavage agents are reported that derive activity from amino acids tethered to a photoactive intercalator.
- Mahon Jr., Kerry P.,Ortiz-Meoz, Rodrigo F.,Prestwich, Erin G.,Kelley, Shana O.
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p. 1956 - 1957
(2007/10/03)
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- Specific Molecular Orbital Contributions to Nucleophilicity. The Thiocarbonyl Group as Privileged Monitor To Pinpoint Active and Less Active Molecular Orbitals in Reactions with Methylating Agents
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The rate constants for 41 compounds bearing a C=S function reacting with MeX (X = I, Tos) span 7 orders of magnitude.The PES spectra of these compounds display two very low energy peaks, which stand clearly apart from the other peaks.These two peaks correspond to the ? orbitals of the C-S group; one is its CS ? bonding orbital oriented out of the molecular plane (?CS) and the other its p-type in-plane lone pair orbital (?S).For some of the compounds, the HOMO is the ?CS orbital and for others the HOMO is the ?S lone pair orbital.The best correlation (R = 0.96) between rate constants k and PES data is obtained when ln(k) is plotted against the inverse of PES energy of the ?S lone pair orbital.Whether this lone pair orbital is the HOMO or the next lower HOMO has no importance.A modest correlation (R = 0.78) is obtained when ln(k) is plotted against the inverse of PES energy of the ?CS bonding orbital.An attempt to correlate the calculated energy of the third highest occupied orbital (from AM1 calculations) with ln(k) provides a complete scattering of data (R S (ca. 90 kcal mol-1 deeper than the HOMO) correlates reasonably with ln(k) (R = 0.88).The energies of the S 2s and 2p core orbitals (calculated for 13 cyclic compounds with the HF/3-21G technique to be 4000 to 5500 kcal mol-1 deeper than HOMO) correlate with ln(k) (R = 0.86) as well as does that of the second lone pair orbital ?S.These results are the first where both frontier orbitals and core orbitals display correlation with overall reactivity.They are discussed in terms of direct (perturbational) versus indirect (nonperturbational) concepts.
- Arbelot, M.,Allouche, A.,Purcell, K. F.,Chanon, M.
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p. 2330 - 2343
(2007/10/02)
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- An ESR Study of the Cation Radicals of Azodibenzothiazolyls
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Methyl and ethyl derivatives of thiobenzothiazole and their quaternary salts were prepared by the sealed glass tube method.Azinodibenzothiazoles were oxidized by lead(IV) acetate, giving cation radical salts with the boron tetrafluoride anion moiety.The well-resolved esr spectra observed were analyzed by comparing the data with those of a deuteriomethylated radical and with those from the MO calculations.Spin density distribution was consistently determined by computer simulation, including almost the same unpaired electron distribution on the four nitrogen atoms.
- Okada, Keiichi,Yamauchi, Jun,Deguchi, Yasuo
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p. 723 - 727
(2007/10/02)
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