164365-88-2Relevant articles and documents
Influence of calcium-induced aggregation on the sensitivity of aminobis(methylenephosphonate)-containing potential MRI contrast agents
Henig, Joerg,Mamedov, Ilgar,Fouskova, Petra,Toth, Eva,Logothetis, Nikos K.,Angelovski, Goran,Mayer, Hermann A.
, p. 6472 - 6481 (2011)
A novel class of 1,4,7,10-tetraazacyclododecane-1,4,7- tris(methylenecarboxylic) acid (DO3A)-based lanthanide complexes with relaxometric response to Ca2+ was synthesized, and their physicochemical properties were investigated. Four macrocyclic ligands containing an alkyl-aminobis(methylenephosphonate) side chain for Ca 2+-chelation have been studied (alkyl is propyl, butyl, pentyl, and hexyl for L1, L2, L3, and L4, respectively). Upon addition of Ca2+, the r1 relaxivity of their Gd3+ complexes decreased up to 61% of the initial value for the best compounds GdL3 and GdL4. The relaxivity of the complexes was concentration dependent (it decreases with increasing concentration). Diffusion NMR studies on the Y3+ analogues evidenced the formation of agglomerates at higher concentrations; the aggregation becomes even more important in the presence of Ca2+. 31P NMR experiments on EuL1 and EuL4 indicated the coordination of a phosphonate to the Ln3+ for the ligand with a propyl chain, while phosphonate coordination was not observed for the analogue bearing a hexyl linker. Potentiometric titrations yielded protonation constants of the Gd 3+ complexes. log KH1 values for all complexes lie between 6.12 and 7.11 whereas log KH2 values are between 4.61 and 5.87. Luminescence emission spectra recorded on the Eu3+ complexes confirmed the coordination of a phosphonate group to the Ln3+ center in EuL1. Luminescence lifetime measurements showed that Ca-induced agglomeration reduces the hydration number which is the main cause for the change in r1. Variable temperature 17O NMR experiments evidenced high water exchange rates on GdL1, GdL2, and GdL3 comparable to that of the aqua ion.
Application of bioorthogonal hetero-Diels-Alder cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid and vinyl thioether for imaging inside living cells
Bazan, Bart?omiej,Pa?asz, Aleksandra,Skalniak, ?ukasz,Cie?, Dariusz,Buda, Szymon,J?drzejowska, Katarzyna,G?omb, Sonia,Kamzol, Daniel,Czarnota, Kinga,Latos, Krystian,Kozie?, Krzysztof,Musielak, Bogdan
supporting information, p. 6045 - 6058 (2021/07/25)
New bioorthogonal cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid as 1-oxa-1,3-butadienes and vinyl thioether as a dienophile has been applied to imaging inside living cells. The reaction is high yielding, selective, and fast in aqueous media. The proposed 1-oxa-1,3-butadiene derivative conjugated to a FITC fluorochrome selectively and rapidly labels the cancer cells pretreated with the dienophile-taxol. The second order rate constants k2 for various proposed bioorthogonal cycloadditions were estimated to be in the range from 0.9 × 10-2 M-1 s-1 to 1.4 M-1 s-1, which is much better than in the case of the first generation TQ-ligation (o-quinolinone quinone methide and vinyl thioether ligation, k2 = 1.5 × 10-3 M-1 s-1) and comparable or better to that for the second generation TQ-ligation (k2 = 2.8 × 10-2 M-1 s-1). The reaction rate constants k2 of proposed ligation reactions are in the range of the rate constants k2 for tetrazines and norbornenes or tetrazines and cyclopropenes. These findings indicate that this chemistry is suitable for in vitro imaging experiments.
Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain
Fiala, Tomas,Wang, Jihang,Dunn, Matthew,?ebej, Peter,Choi, Se Joon,Nwadibia, Ekeoma C.,Fialova, Eva,Martinez, Diana M.,Cheetham, Claire E.,Fogle, Keri J.,Palladino, Michael J.,Freyberg, Zachary,Sulzer, David,Sames, Dalibor
supporting information, p. 9285 - 9301 (2020/06/04)
Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. The impact of these highly lipophilic sensors has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a nongenetic molecular platform for cell- and molecule-specific targeting of synthetic VSDs in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of VSDs by dynamic encapsulation and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.
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Page/Page column 26; 27, (2020/06/19)
Novel antimicrobial inhibitors of Biotin Protein Ligase (BPL), which incorporate biotin, are described. The inhibitors have a structure that inhibit the essential metabolic enzyme BPL of pathogens and have been shown to be stable in whole blood and effect
