A5058745537- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- SARS-CoV-2 and COVID-19 Research
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Synthesis of β-Lactam Compounds
- Radiopharmaceutical Chemistry and Applications
- Bladder and Urothelial Cancer Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- COVID-19 Clinical Research Studies
University of Freiburg
2020-2023
University of Göttingen
2020-2022
Universitätsmedizin Göttingen
2020-2022
Two proteases produced by the SARS-CoV-2 virus, main protease and papain-like protease, are essential for viral replication have become focus of drug development programs treatment COVID-19. We screened a highly focused library compounds containing covalent warheads designed to target cysteine identify new lead scaffolds both Mpro PLpro proteases. These efforts identified small number hits no viable protease. Of as inhibitors purified recombinant only two inhibited infectivity in cellular...
Abstract N‐terminal sequences are important sites for post‐translational modifications that alter protein localization, activity, and stability. Dipeptidyl peptidase 9 (DPP9) is a serine aminopeptidase with the rare ability to cleave off dipeptides imino acid proline in second position. Here, we identify tumor‐suppressor BRCA2 as DPP9 substrate show this interaction be induced by DNA damage. We present crystallographic structures documenting intracrystalline enzymatic activity of DPP9,...
Abstract Dipeptidyl peptidases 8 and 9 (DPP8/9) have gathered interest as drug targets due to their important roles in biological processes like immunity tumorigenesis. Elucidation of distinct individual functions remains an ongoing task could benefit from the availability novel, chemically diverse selective chemical tools. Here, we report activity‐based protein profiling (ABPP)‐mediated discovery 4‐oxo‐β‐lactams potent, non‐substrate‐like nanomolar DPP8/9 inhibitors. X‐ray crystallographic...
ABSTRACT Two proteases produced by the SARS-CoV-2 virus, M pro and PL , are essential for viral replication have become focus of drug development programs treatment COVID-19. We screened a highly focused library compounds containing covalent warheads designed to target cysteine identify new lead scaffolds both proteases. These efforts identified small number hits protease no viable protease. Of as inhibitors purified recombinant protease, only two inhibited infectivity in cellular infection...
Summary Dipeptidyl peptidase 9 ( DPP9) is a serine protease cleaving N-terminal dipeptides preferentially post-proline with (patho)physiological roles in the immune system and cancer. Only few DPP9 substrates are known. Here we identify an association of human tumour suppressor BRCA2, key player repair DNA double-strand breaks that promotes formation RAD51 filaments. This interaction triggered by DNA-damage requires access to active-site. We present crystallographic structures documenting...
Abstract Die Dipeptidylpeptidasen 8 und 9 (DPP8/9) sind aufgrund ihrer wichtigen Rolle in biologischen Prozessen wie der Immunität Tumorgenese den letzten Jahren Fokus Wirkstoffforschung gerückt. Der individuelle Beitrag jeweiligen Protease innerhalb dieser Prozesse ist bisher jedoch meistens noch unbekannt. Untersuchung individuellen Funktion kann dabei von Verfügbarkeit Protease‐selektiver chemisch‐diverser Hemmstoffe profitieren. In Arbeit stellen wir die durch Anwendung...
Ein einsames 4-Oxo-β-lactam-Molekül bewegt sich in Richtung des katalytischen Zentrums einer Dipeptidylpeptidase 8 (DPP8) einem Universum an chemischem Raum. Die Erzielung DPP8/9-Selektivität ist nach wie vor eine Herausforderung für die chemische Biologie. 4-Oxo-β-lactame, mithilfe Chemoproteomics-Plattform als DPP8/9-Inhibitoren identifiziert wurden, könnten der Schlüssel zur gesuchten über einen präzedenzlosen DPP8-spezifischen Mechanismus sein, Markus Kaiser, Rui Moreira et al. ihrem...