Chemical Biology

The Laboratory of Medicinal Chemistry University of Antwerp (UAMC)

• Prof. Koen Augustyns
• Prof. Pieter Van der veken
• Prof. Hans De Winter

UAMC has established  ChemProTools, a technology platform to develop selective chemical probes and analytical methodology for the study of enzyme activity in different matrices

1. Design and synthesis of selective activity based probes
2. Evaluation of the probes on different enzyme families
3. In collaboration with the proteomicsgroup of Prof. Kris Gevaert (VIB/UGent) we developped technologies to measure and monitor probe:enzyme complexes in different matrices
4. In collaboration with MICA, University of Antwerp we have access to bio-imaging facilities

Preferably you deliver the target enzyme and the matrix in which the probe should be monitored. For in vivo evaluation we depend on the models of our partners or customers.

link to website

ChemProTools

Laboratory of Chemical Biology (KU Leuven)

• Prof. Steven Verhelst

Our research group works on the development and application of small molecule chemical tools for chemical biology and chemical proteomics. We focus on three different areas:

1. We synthesize activity-based probes and other covalent modifyers that tag proteins according to a certain trait (e.g. an activity or a post-translational modification). Different techniques are utilized for the detection of these covalent complexes, including tandem mass spectrometry, gel-based analysis and fluorescent microscopy.

2. One of our primary targets are proteases, in particular intramembrane proteases. Using chemical tools, we aim to elucidate the biochemical mechanism and biological function, and determine whether these enzymes may be used as a future target for drug development.

3. We design and utilize cleavable linker in order to better identify the targets of covalent probes by tandem mass spectrometry methods.

keywords: organic synthesis, solid phase peptide synthesis, activity-based probes, click chemistry, proteases, intramembrane proteases, target discovery, proteomics.

link to website: www.verhelstlab.net

Laboratory for Medicinal Chemistry (UGent)

• Prof. Serge Van Calenbergh

There is a strong need for small molecule profiling tools for several reasons:

• the molecular target of a compound identified in drug screens is not always known (e.g. in phenotypic screens) yet indispensable for its further development;
• adverse drug reactions are often related to off-target binding and in order to prevent or remedy this in the course of the chemical optimization of a compound, knowledge of alternative protein targets is essential;
• in addition, drug target profiling is an important tool in drug repositioning efforts.

As a consequence, virtually every drug discovery project will require target profiling services at a certain stage.

To address this need, a small molecule target profiling platform has been established. has been set up based on the MASPIT cell array screening technology. MASPIT, for MAmmalian Small molecule-Protein Interaction Trap, is a proprietary three-hybrid approach that enables the identification of interactions between small organic compounds and proteins in living human cells, developed in the Cytokine Receptor Laboratory (Jan Tavernier, Sam Lievens). The Laboratory for Medicinal Chemistry supports the synthetic part of this technology, i.e. the synthesis of “bait” conjugates, on which MASPIT relies on.

www.medchem.ugent.be

Laboratory for Organic and Bioorganic Synthesis (UGent)

• Prof. Johan Van der Eycken

Synthesis of novel fluorescent probes for labeling of biomolecules and gene reporting: our fluorizers possess a remarkable photostability, rendering them ideal for long term experiments, and also show a large Stokes shift, avoiding background fluorescence interference. Their absorption and emission wavelength can be tuned by varying the substituents.

link to the website

Organic Synthesis Research Group (UGent)

• Prof. Johan Winne
• Em. Prof. Pierre De Clercq

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.

1. The chemical synthesis part mainly involves the development of novel strategies and methods to assemble complex scaffolds, focusing on multiple bond forming steps such as cycloadditions and cascade reactions.
2. For the chemical derivatisation part, the group focuses on the development of application-oriented versatile covalent ligation reactions to generate multiple derivatives from a single synthetic intermediate.
3. As a major theme in the recent research, that encompasses both of the above general research topics, the group has started to design and target highly modular synthetic building blocks that allow a rapid exploration of Natural Product-like chemical space using simple and orthogonal functional group transformations.
4. The concepts of versatile ligation reactions and modular building blocks in organic synthesis are also explored and applied in various collaborative research projects going from macromolecular and materials science to chemical biology.

Chemical expertise keywords: terpenes, furans, carbocationic processes, fused polycyclic systems, stereochemistry, cycloadditions, click chemistry, natural products, organic reactivity

link to the website

Organic and Biomimetic Research Chemistry (UGent)

• Prof. Annemieke Madder

The Organic and Biomimetic Chemistry Research Group has consistently found its inspiration in naturally occurring systems and biologically relevant processes. As major research interests that have been followed up until this time the following research lines can be defined:

a) The design and synthesis of artificial hydrolases where both modified multipodal oligopeptides and modified oligonucleotide duplexes are used in order to mimic the desired catalytic site.

b) The construction of conformationally defined multipodal peptide architectures. Methods are being developed for the synthesis of both dipodal and tripodal peptides on solid phase. The synthesized compounds can possibly find applications as peptide vaccins, DNA-binding ligands and receptor mimics. More specifically the use of cholic acid based steroid derivatives has been explored for the conformational restriction and metabolic stabilization of appended peptide chains in the development of novel transcription factor models with DNA binding capacity.

c) The development of new methods for crosslinking of biomacromolecules such as peptides, proteins and oligonucleotides. Through the use of a furan moiety with inducible reactivity a method was developed for the site-selective introduction of covalent bonds between two binding partners.

link to the website