Structure–activity relationship studies of the natural product cystobactamid at four different positions led to novel imaging probes and analogs with superior antibacterial activities and in vivo efficacy.

Branching out: Novel branched ubiquitin isopeptide activity‐based probes (UIPPs) were engineered to profile ubiquitin (Ub) linkage specificity of deubiquitinating enzymes (DUBs) in cell extracts. Using chemical proteomics, a preference towards K48‐linked Ub was shown for USP5, USP7, UCH L‐3, and UCH L‐5, whereas USP19 and USP38 preferred K63‐linked Ub.

Ratjadone derivatives have been successfully introduced as suitable payloads with new mode of action for targeted drug conjugates.

The rise of antibiotic resistance causes a serious health care problem, and its counterfeit demands novel, innovative concepts. The combination of photopharmacology, enabling a light-controlled reversible modulation of drug activity, with antibiotic drug design has led to first photoswitchable antibiotic compounds derived from established scaffolds. In this study, we converted cystobactamids, gyraseinhibiting natural products with an oligoaryl scaffold and highly potent antibacterial activities, into photoswitchable agents by inserting azobenzene in the N-terminal part and/or an acylhydrazone moiety near the C-terminus, yielding twenty analogs that contain mono-as well as double-switches. Antibiotic and gyrase inhibition properties could be modulated 3.4-fold and 5-fold by light, respectively. Notably, the sensitivity of photoswitchable cystobactamids towards two known resistance factors, the peptidase AlbD and the scavenger protein AlbA, was light-dependent. While irradiation of an analog with an N-terminal azobenzene with 365 nm light led to less degradation by AlbD, the AlbAmediated inactivation was induced. This provides a proof-ofprinciple that resistance towards photoswitchable antibiotics can be optically controlled.

Amines Q 0120Hydrogen Bond Catalyzed Direct Reductive Amination of Ketones. -The first example which exclusively relies on hydrogen bonding for imine activation is demonstrated. -(MENCHE*, D.; HASSFELD, J.; LI, J.; MENCHE, G.; RITTER, A.; RUDOLPH, S.; Org. Lett. 8 (2006) 4, 741-744; Ges. Biotechnol. Forsch. mbH, D-38124 Braunschweig, Germany; Eng.) -R. Steudel 26-069