• Targeted medicinal chemistry towards antibiotics and anti-cancer compounds.
• Focus on compounds with aim to overcome drug-resistance
• Yuri Ermolovich, Post doc
• Niranjan Thota , Post doc
• Emil Rørsted Pedersen, Research Assistant
• Jerry Herrington, MSc
Current selected projects
Metallo-β-lactamase inhibitors: Enabling antibiotics to combat multidrug resistant bacteria.
Carbapenemes are bactericidal β-lactam antimicrobials (BLA) with proven efficacy in severe infections caused by extended spectrum β-lactamase (ESBL) producing bacteria.
However, the efficacy of BLAs is increasingly threatened by, among others, widespread dissemination of β-lactamases, catalyzing hydrolysis and inactivation of BLA
Aim is to extend and/or prolong the utility of meropenem as β-lactam antibiotic, known as the “last resort drug” for the treatment of Gram-negative bacteria expressing MBLs. In this major collaborative H2020/IMI project the objective is to optimize a series of novel metallo β-lactamase (MBL) inhibitors as β-lactam antibiotic adjuvants.
Many diseases are related to defects in ribosomes. These ribosomopathies, although involving ubiquitous fundamental cellular processes, display various clinical manifestations such as short stature, cancer predisposition or haematological disorders. Thus, despite their differences at a clinical level they affect the same biochemical process. The ribosome is an attractive and well characterised drug target. For instance, many antibiotics exploit minor structural differences to selectively target bacterial (prokaryotic) ribosomes. However, designing compounds capable of altering dysfunctional eukaryotic ribosomes remains a challenge and constitutes a largely unexplored territory. The project is based on the hypothesis that specific pathogenic processes are associated with certain ribosome modifications and subsequent changes in translations. Interfering with these modifications is expected to hinder the disease specific changes in translation and thereby alter the disease. Thus, the ultimate goal is to discover ligands selectively targeting post-transcriptionally modified ribosomes. This will be explored using a multidisciplinary approach combining computational modelling, medicinal chemistry and biochemistry.