124529-64-2Relevant articles and documents
Synthesis, Biological Evaluation, and Utility of Fluorescent Ligands Targeting the μ-Opioid Receptor
Schembri, Luke S.,Stoddart, Leigh A.,Briddon, Stephen J.,Kellam, Barrie,Canals, Meritxell,Graham, Bim,Scammells, Peter J.
, p. 9754 - 9767 (2015)
Fluorescently labeled ligands are useful pharmacological research tools for studying receptor localization, trafficking, and signaling processes via fluorescence imaging. They are also employed in fluorescent binding assays. This study is centered on the design, synthesis, and pharmacological evaluation of fluorescent probes for the opioid receptors, for which relatively few non-peptidic fluorescent probes currently exist. The known μ-opioid receptor (MOR) partial agonist, buprenorphine, was structurally elaborated to include an amidoalkylamine linker moiety that was coupled with a range of fluorophores to afford new fluorescent probes. All compounds proved to be selective MOR antagonists. Confocal fluorescence microscopy studies revealed that the probe incorporating a sulfonated cyanine-5 fluorophore was the most appropriate for imaging studies. This ligand was subsequently employed in an automated fluorescence-based competition binding assay, allowing the pKi values of several well-known opioid ligands to be determined. Thus, this new probe will prove useful in future studies of MOR receptor pharmacology.
Efficient Synthesis of a Family of Bifunctional Chelators Based on the PCTA[12] Macrocycle Suitable for Bioconjugation
Leygue, Nadine,Enel, Morgane,Diallo, Abdel,Mestre-Voegtlé, Béatrice,Galaup, Chantal,Picard, Claude
, p. 2899 - 2913 (2019/05/15)
PCTA[12] is a 12-membered tetraaza-macrocyclic ligand that incorporates a pyridine unit within the macrocyclic ring and three acetate pendant arms. Unlike DOTA and NOTA chelators, PCTA is a recent entry to the field of macrocyclic polyaminocarboxylate ligands available to complex a variety of M2+/M3+ ions for biomedical applications such as diagnostic and radiotherapeutic. Despite the promising properties of its chelates, only a few of bifunctional chelating agents (BFCAs) derived from PCTA have been described so far. Based on our very recent methodology for the preparation of PCTA[12] itself, we report here the efficient synthesis of several BFCAs derived from PCTA bearing a free reactive function group, mainly devoted to conjugation purposes: ester, carboxylic acid, alcohol, aliphatic amine, aromatic amine, maleimide, bromo or azide functions. These functions were introduced either on the 4-position of the pyridine ring or on the methylene carbon atom of the central acetate chelating arm, while keeping the three carboxylate groups available for metal chelation. Moreover, two of these BFCAs-PCTA were used for conjugation with a tetrapeptide (cholecystokinin analogue), a bioactive molecule (biotin), or a solid support (silica gel).
Functionalized phosphonated half-cage molecules as ligands for metal complexes
Villemin, Elise,Herent, Marie-France,Marchand-Brynaert, Jacqueline
supporting information, p. 6165 - 6178 (2013/01/15)
Phosphonated molecules, featuring a half-cage structure and a N-lateral chain with additional metal coordinating groups were designed as ligands of metal cations. These compounds were synthesized by a Diels-Alder (DA) strategy, using 1-diethoxyphosphoryl-1,3-butadiene and a series of N-substituted maleimides as dienophiles. Two cycloadducts, bearing a terminal primary alcohol and a terminal iodide, respectively, were used as key intermediates for further functionalizations. Metal coordination properties of the ligands equipped with functionalized N-lateral chains were proven by an ESI-HRMS study. The stoichiometry of one selected EuIII complex with a diphosphonated ligand was determined by photoluminescence spectroscopy in emission mode.
