Tuning the Polarity of Antibiotic‐Cy5 Conjugates Enables Highly Selective Labeling of Binding Sites

Multidrug‐resistant bacteria pose a major threat to global health, even as newly introduced antibiotics continue to lose their therapeutic value. Against this background, deeper insights into bacterial interaction with antibiotic drugs are urgently required, whereas fluorescently labeled drug conjugates can serve as highly valuable tools. Herein, the preparation and biological evaluation of 13 new fluorescent antibiotic‐Cy5 dye conjugates is described, in which the tuning of the polarity of the Cy5 dye proved to be a key element to achieve highly favorable properties for various fields of application.A systematic study on 13 new antibiotic‐Cy5 dye conjugates derived from ampicillin, erythromycin, trimethoprim, and vancomycin revealed that in particular the incorporation of Cy5 dyes of low polarity leads to significantly improved properties regarding photostability, optical brightness, and distinctiveness. In turn, the related conjugates could be identified as outstanding tools for a variety of studies including fluorescence and super‐resolution spectroscopy, differentiation of Gram+/‐ bacteria and competition binding. image Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Deutsche Bundesstiftung Umwelt http://dx.doi.org/10.13039/10000763

Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine‐Derived Phenylazocarboxamides as Novel μ‐Opioid Receptor Ligands

Targeted structural modifications have led to a novel type of buprenorphine‐derived opioid receptor ligand displaying an improved selectivity profile for the μ‐OR subtype. On this basis, it is shown that phenylazocarboxamides may serve as useful bioisosteric replacements for the widely occurring cinnamide units, without loss of OR binding affinity or subtype selectivity. This study further includes functional experiments pointing to weak partial agonist properties of the novel μ‐OR ligands, as well as docking and metabolism experiments. Finally, the unique bifunctional character of phenylazocarboxylates, herein serving as precursors for the azocarboxamide subunit, was exploited to demonstrate the accessibility of an 18F‐fluorinated analogue