26392-97-2Relevant academic research and scientific papers
Demonstrating Ligandability of the LC3A and LC3B Adapter Interface
Hartmann, Markus,Huber, Jessica,Kramer, Jan S.,Heering, Jan,Pietsch, Larissa,Stark, Holger,Odadzic, Dalibor,Bischoff, Iris,Fürst, Robert,Schr?der, Martin,Akutsu, Masato,Chaikuad, Apirat,D?tsch, Volker,Knapp, Stefan,Biondi, Ricardo M.,Rogov, Vladimir V.,Proschak, Ewgenij
, p. 3720 - 3746 (2021/05/04)
Autophagy is the common name for a number of lysosome-based degradation pathways of cytosolic cargos. The key components of autophagy are members of Atg8 family proteins involved in almost all steps of the process, from autophagosome formation to their selective fusion with lysosomes. In this study, we show that the homologous members of the human Atg8 family proteins, LC3A and LC3B, are druggable by a small molecule inhibitor novobiocin. Structure-activity relationship (SAR) studies of the 4-hydroxy coumarin core scaffold were performed, supported by a crystal structure of the LC3A dihydronovobiocin complex. The study reports the first nonpeptide inhibitors for these protein interaction targets and will lay the foundation for the development of more potent chemical probes for the Atg8 protein family which may also find applications for the development of autophagy-mediated degraders (AUTACs).
Sequential meta-/ortho-C-H Functionalizations by One-Pot Ruthenium(II/III) Catalysis
Korvorapun, Korkit,Kaplaneris, Nikolaos,Rogge, Torben,Warratz, Svenja,Stückl, A. Claudia,Ackermann, Lutz
, p. 886 - 892 (2018/02/14)
Sequential twofold meta-C-H/ortho-C-H functionalization was achieved by means of versatile ruthenium(II) biscarboxylate catalysis. The double C-H activation proved viable in a one-pot fashion with the assistance of synthetically useful imidates. The operationally simple twofold C-H functionalization occurred with high levels of positional selectivity control and was conducted in a nonsequential manner by the judicious choice of the reaction temperature. Detailed experimental mechanistic studies, including unprecedented electron paramagnetic resonance (EPR) experiments, provided strong support for homolytic C-X bond cleavage and facile C-H ruthenation, while a computational density functional theory (DFT) analysis was supportive of a novel mechanistic scenario involving synergistic catalysis via cyclometalated ruthenium(III) complexes as key intermediates.
