Exploring Chemical Activation
Prof. Ben FERINGA
UNIVERSITY OF GRONINGEN, Groningen, The Netherlands
The Synthesis of Functional Molecular Systems
- Combining Covalent and Non-Covalent Synthesis -
Prof. Bert MEIJER
EINDHOVEN UNIVERSITY OF TECHNOLOGY, Eindhoven, The Netherlands
The ambition to construct complex molecular systems, materials and soft matter is driven by a need for technological evolution and our intrinsic curiosity to comprehend the origin of life. Supramolecular chemists aim to tackle this challenge using a combination of covalent and non-covalent reaction steps leading to multi-component systems with emerging complexity. Yet, such complex synthesis strategies often coincide with increasingly difficult reaction schemes and a narrow window of suitable reaction conditions. Alike small details that drive the unrepeatable crystallization of a desired polymorph or a sudden drop in reactivity of a catalyst from a different source, recently also supramolecular chemistry reached a level of fine-tuning in which underappreciated subtleties can have an unexpected major impact on a system. In the lecture, examples of our group are used to highlight the impact of subtle “irregularities” on supramolecular systems. Based on effects of pathway-complexity and minute impurities in organic solvents or the supramolecular building block we discuss potential pitfalls in the synthesis of soft matter. It is meant to sensitize for often overlooked details and to stimulate a discussion about reproducibility issues in supramolecular chemistry and soft matter.
ChemBioProbes for Labeling, Visualizing and Manipulating Biological Function
Dr Johannes BROICHHAGEN
LEIBNIZ-FORSCHUNGSINSTITUT FÜR MOLEKULARE PHARMAKOLOGIE (FMP), Leibniz, Germany
Selective targeting of biomolecules for labeling, visualization and functional manipulation is at the forefront of Chemical Biology. To tackle challenges by interrogation and analysis of biomolecules in a selective and quantitative manner, we employ approaches from photopharmacology, custom-tailored labelling techniques and fluorophore design. Our latest generation of photoswitches enable reversible on/off remote control of metabotropic glutamate receptor 2 (mGluR2), a class C G Protein Coupled Receptor (GPCR) involved in neurotransmission, while we perform specific labeling in cellular compartments to differentiate functional receptor pools. With our deuterated fluorophores that show increased fluorescent lifetimes, higher photostability and augmented brightness, we pave the way for new applications in nanoscopy and single molecule tracking.
Fluorogenic Probes for Background-free Imaging of GPCRs in Living Cells and in vivo
Dr Julie KARPENKO
UNIVERSITY OF STRASBOURG, Strasbourg, France
Fluorogenic probes, which increase their fluorescence in response to a certain change in the microenvironment, are powerful tools in bioimaging. They allow for direct detection of analytes without removal of the unbound probe and thus for in situ monitoring of biomolecular interactions. In our laboratory, we have demonstrated the power of receptor-specific fluorogenic probes to image unmodified G protein-coupled receptors in their native environment in living cells and in living animals.
Pattern-Generating Fluorescent Molecular Probes for Chemical Biology
Dr Leila MOTIEI
WEIZMANN INSTITUTE OF SCIENCE, Rehovot, Israel
In my talk, I will give an overview of a new class of fluorescent molecular probes recently developed in our group, and show how they can be used to detect individual proteins, protein combinations, as well as binding interactions and dynamic changes that occur on their surfaces. Specifically, I will show how such fluorescent probes can be used to identify combinations of specific protein families within complex biological settings as well as inside living cells.
Cyclophellitol, a Natural Product Glucosidase Inhibitor, as a Starting Point for Activity-based Protein Profiling
Prof. Hermen OVERKLEEFT
UNIVERSITY OF LEIDEN, Leiden, The Netherlands
Cyclophellitol, isolated in 1990 from Phellinus sp., is a mechanism-based, covalent and irreversible retaining beta-glucosidase inhibitor. Since its discovery, effective routes of synthesis towards cyclophellitol have been developed and adapted to produce configurational and functional analogues. Mechanism-based enzyme inhibitors have formed the starting point in the past decades in the development of activity-based probes for the study of various enzyme families (serine hydrolases, proteases) in chemical proteomics approaches. In this contribution I will discuss the merits of the cyclophellitol scaffold for the development of a suite of probes targeting various retaining glycosidases, and their use in the discovery of glycoprocessing enzyme targeting inhibitors.