TY  - JOUR
A1  - Christian, Gentzsch
A1  - Seier, Kerstin
A1  - Drakopoulos, Antonios
A1  - Jobin, Marie-Lise
A1  - Lanoiselée, Yann
A1  - Koszegi, Zsombor
A1  - Maurel, Damien
A1  - Sounier, Rémy
A1  - Hübner, Harald
A1  - Gmeiner, Peter
A1  - Granier, Sébastien
A1  - Calebiro, Davide
A1  - Decker, Michael
T1  - Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization
JF  - Angewandte Chemie International Edition
N2  - μ‐Opioid receptors (μ‐ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ‐ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ‐OR antagonist E‐p‐nitrocinnamoylamino‐dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single‐molecule imaging of μ‐ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ‐ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ‐ORs interact with each other to form short‐lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ‐OR pharmacology at single‐molecule level.
KW  - single-molecule microscopy
KW  - fluorescent probes
KW  - G-protein coupled receptor
KW  - homodimerization
KW  - opioid ligands
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212398
VL  - 59
IS  - 15
ER  - 
TY  - JOUR
A1  - Sawatzky, Edgar
A1  - Drakopoulos, Antonios
A1  - Rölz, Martin
A1  - Sotriffer, Christoph
A1  - Engels, Bernd
A1  - Decker, Michael
T1  - Experimental and theoretical investigations into the stability of cyclic aminals
JF  - Beilstein Journal of Organic Chemistry
N2  - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking.

Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom.

Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account.
KW  - quantum mechanics
KW  - hydrolysis
KW  - kinetics
KW  - molecular mechanics
KW  - natural products
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976
VL  - 12
ER  - 
TY  - JOUR
A1  - Drakopoulos, Antonios
A1  - Decker, Michael
T1  - Development and Biological Applications of Fluorescent Opioid Ligands
JF  - ChemPlusChem
N2  - Opioid receptors (ORs) are classified among the oldest and best investigated drug targets due to their fundamental role in the treatment of pain and related disorders. ORs are divided in three conventional subtypes (μ, κ, δ) and the non‐classical nocicepetin receptor. All ORs are family A G protein‐coupled receptors (GPCRs), and are located on the cell surface. Modern biophysical methods use light to investigate physiological processes at organismal, cellular and subcellular level. Many of these methods rely on fluorescent ligands, thus highlighting their importance. This review addresses the advancements in the development of opioid fluorescent ligands and their use in biological, pharmacological and imaging applications.
KW  - biophysics
KW  - fluorescent ligands
KW  - imaging
KW  - microscopy
KW  - opioid receptors
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216068
VL  - 85
IS  - 6
SP  - 1354
EP  - 1364
ER  -