Mechanism of action

Albicidin is a peptide antibiotic that has shown great promise for inhibiting DNA topoisomerase of fluoroquinolone-resistant Gram-negative pathogens, but its mode of action is not fully clear. Now, cryoelectron microscopy structures of albicidin–gyrase complexes provide detailed insights into the mechanism of this natural product.

Tropolones harbor a non-benzenoid aromatic scaffold and display a wide-range of bioactivities, however, the cyclic derivatives of aminotroponimines remain underexplored. Here, the authors develop a one-pot synthesis of N^Alkyl/C^Aryl-substituted cyclic-aminotropiminium carboxylate derivatives with promising anticancer properties.

How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.

Native mass spectrometry has been used to interrogate both biased signalling and allosteric modulation of the β₁-adrenergic receptor. Simultaneously capturing the effects of ligand binding and receptor coupling to different G proteins has enabled the relative importance of specific interactions to be investigated.