Medicinal chemistry is a chemistry-based discipline, also involving aspects of biological, medical and pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and preparation of biologically active compounds, the study of their metabolism, the interpretation of their mode of action at the molecular level and the construction of structure-activity relationships.
The Laboratory of Medicinal Chemistry at the KULeuven is part of the Rega institute, an interfacultary research institute focusing on virology, bacteriology, immunology and medicinal chemistry. It is a multidisciplinary laboratory with a focus on organic synthesis, biochemistry, molecular modeling, and analytical techniques such as Mass Spectroscopy and Nuclear Magnetic Resonance (NMR). NMR is likewise also used for structural biology projects. The lab is mostly known for its research on the synthesis and biological evaluation of modified nucleosides, nucleotides and oligonucleotides. In recent years, research has expanded towards the synthesis of novel and drug-like heterocycles. From a therapeutic standpoint of view, our main interest is situated in the field of infectious diseases (viral and bacterial infections), and immunological disorders.
The research of the Group for Organic Chemistry (ORGC) at the VUB, headed by Prof. Steven Ballet and Prof. Guido Verniest, focuses on the synthesis of modified peptides as well as low molecular weight molecules (small molecules) and the development of new synthetic methods for application in medicinal and materials chemistry. The ORGC collaboration network constitutes a platform for the thorough and efficient characterization of the chemical (3D) structure, but also for the determination of the in vitro and in vivo bioactivity of the prepared compounds.
The research unit has established a long standing tradition in the preparation of modified peptides and applications thereof, under the direction of Prof. em. Dirk Tourwé. Being appointed as an associate professor at the VUB, and being trained in the ORGC group, Prof. Steven Ballet carries this research on, making use of the gained expertise. With further support of Prof. Guido Verniest, the group also has expertise in the development of new synthetic methodology, mainly in the field of non-peptide heterocycles, alkyne transformations and late transition metal catalysis. ORGC is an interdepartmental research unit (Department of Chemistry and Department of Bioengineering Sciences) with strong links to the Faculty of Pharmacy and Medicine and the Faculty of Engineering of the VUB.
The Laboratory for Medicinal Chemistry at the UGent belongs to the Faculty of Pharmaceutical Sciences. It mainly concentrates on the development of small molecule modulators of new (i.e., yet unexplored by approved drugs) targets. These modulators can be both enabling chemical tools to interrogate biology or therapeutically useful compounds. From a chemical point of view, much of our work is centered on the chemical synthesis of novel nucleoside and sphingolipid analogues. Our research interest also includes carbohydrate, phosphonate and bioconjugate chemistry. Several of the running projects deal with the design of new lead structures for the treatment of infectious diseases with unmet medical needs (malaria, TB, MRSA) and immunune diseases.
The major research lines in the Medicinal Chemistry group all deal with design, synthesis and characterisation of biologically active, small organic molecules and applying these molecules in models of human pathology. While dedication in this area is highly focused on enzymological targets and includes both reversible and irreversible modifiers of enzymatic activity, our group has over the years gathered singular expertise with covalent and irreversible types of enzyme inhibitors. Compounds with such a mechanism of action are not only investigated for their powerful inhibitory effect per se, but also for their potential to serve as probe molecules in chemical biology and biomarker research.
The Laboratory for Synthesis, Bioresources and Bio-organic Chemistry (SynBioC) at UGent belongs to the Faculty of Bioscience Engineering. The SynBioC group has a broad range of collaborations with laboratories that are extensively testing the synthesized molecules. Innovative scaffolds and natural product analogues are screened in different activity domains (depending on the types of compounds). Compounds are being tested in oncology, analgesic, parasitic, fungicidal and bactericidal applications. In this research also SAR studies and SAR modelling is performed in order to increase the success in the development of biological active structures.
- Total synthesis of complex natural products.
One of the core expertises of the group is the total synthesis of complex natural products with biological activity and their analogues. Peloruside A has recently been isolated from a marine sponge and displays strong activity against cancer cells, comparable to the potent anti-tumor drug taxol. Our research group is trying to develop a flexible synthesis allowing to obtain also other stereoisomers, in order to discover more potent analogues, while at the same time gaining a better insight in the structure-activity relationship. Moreover, we are also developing active analogues with a simplified structure.
The widespread use of antibiotics has induced resistance in the majority of pathogenic bacteria, rendering inefficient common antibiotics like penicillins and tetracyclines. Consequently, the development of novel antibiotics to fight life-threatening diseases is a matter of top priority for the pharmaceutical industry nowadays. The disruption of the biosynthesis of the bacterial cell wall, the so-called peptidoglycan, is a very attractive strategy for the development of antibiotics. Although a lot of attention has been focused on inhibition of the peptidoglycan cross-linking enzymes (e.g. by penicillins), an almost unexplored yet highly promising alternative involves the inhibition of the enzymes responsible for the build-up of the polysaccharide backbone. In our search towards powerful innovative antibiotics we are working on the development of new types of transglycosylase inhibitors based on the enzyme binding interactions of both the substrate (lipid II) and the naturally occurring inhibitor moenomycin.
- Design and synthesis of novel privileged scaffolds.
Although several peptides possess a strong biological activity, their low bio-availability due to their poor solubility and their sensitivity to proteolytic enzymes renders them unsuitable as drug candidates. An efficient solution to this problem is the development of small peptidomimetics composed of a central scaffold, decorated with those side chains which in the active peptide are responsible for the interaction with the receptor. Our lab is involved in the development of novel privileged scaffolds, which can be valorized against varying targets by decoration with the proper side chains.
The main focus of the Organic Synthesis Research Group of UGent (Faculty of Science) is the chemical synthesis and derivatisation of target compounds with non-trivial carbon connectivities, such as those found in polycyclic Natural Products.
Chemical expertise keywords: terpenes, furans, carbocationic processes, fused polycyclic systems, stereochemistry, cycloadditions, click chemistry, natural products, organic reactivity