Section for Organic and Medicinal Chemistry
«With our medicinal chemistry expertise, structure-based design and organic synthesis, we develop new treatment options for patients.»
The research activities of the section for Organic and Medicinal Chemistry are focused on the organic synthesis and analyses of functional molecules at the interface between chemistry and biology with an emphasis on the development of clinical drug candidates for therapeutically relevant indications.
Areas of expertise
Medicinal Chemistry
Our Medicinal Chemistry activities span from hit identification, through hit to lead development and lead optimization to delivering active pharmaceutical ingredients (APIs) for in vitro and in vivo studies. Our focus is on the development of clinical candidates with our industry partners and includes the structural analysis of the target proteins (and their complexes) and results in the delivery of novel and patentable small organic ligands for clinical trials by using a combination of classical SAR profiling and state of the art fragment-based approaches.
- structural analysis of the target protein (X-ray analysis of co-crystal structures)
- NMR binding studies (ligand/protein)
- fragment-based design of novel ligands
- effective application of industry standard docking software
- multi-step organic synthesis of ligands
- establishment of structure activity relationships (SAR)
- development of data bank based IT solutions for the information management of chemical and biological data (SAR, inventory, etc.)
Coverstory: De novo Design by Metamorphosis
ZHAW-Medienmitteilung (German): ChemMedChem about the de novo design and synthesis of protease inhibitors (11.3.2015).
Selected publications
- Chellat, Mathieu; Raguž, Luka; Riedl, Rainer "Targeting Antibiotic Resistance" Angew. Chem. Int. Ed. 2016, 55, 6600-6626; Angew.Chem. 2016, 128, 6710–6738.
- Fischer, Thomas; Riedl, Rainer "Molecular recognition of the catalytic zinc (II) ion in MMP-13: Structure-based evolution of an allosteric inhibitor to dual binding mode inhibitors with improved lipophilic ligand efficiencies" invited article for the Special Issue "Enzyme-Inhibitor Interaction as Examples of Molecular Recognition" Int. J. Mol. Sci. 2016, 17, 314. Front cover story 3/2016.
- Lanz, Jan; Riedl, Rainer "Merging Allosteric and Active Site Binding Motifs: De novo Generation of Target Selectivity and Potency via Natural-Product-Derived Fragments" ChemMedChem. 2015, 10, 451–454. Front cover story 3/2015.
- Fischer, Thomas; Riedl, Rainer "Strategic Targeting of Multiple Water-Mediated Interactions: A Concise and Rational Structure-Based Design Approach to Potent and Selective MMP-13 Inhibitors" ChemMedChem. 2013, 8, 1457-1461. Cover story 9/2013.
- ZHAW News Release on review article on targeting antibiotic resistance published in Angewandte Chemie (8.6.2016, in German).
- ZHAW News Release on cover story about the development of protease inhibitors with a dual binding motif in the International Journal of Molecular Sciences (3.5.2016, in German).
- ZHAW News Release on cover story about the de novo design and synthesis of protease inhibitors based on natural product fragments in ChemMedChem (11.3.2015, in German).
Organic Synthesis + Synthetic Methodology
Our activities in the area of Organic Synthesis and Synthetic Methodology are focused around the multi-step syntheses of catalysts and APIs. Our core competence in Organic Synthesis and implementation of computational chemistry allow for a flexible research strategy for catalyst development and drug discovery. This flexible and multi-faceted approach has been applied with great success to the benefit of our industry
partners.
In addition to classical organic synthetic techniques we have invested in advanced organic synthetic technologies such as microwave reactors, microreactors, parallel synthesis, automated solid phase synthesizers and high pressure reactors.
National Research Consortium for drug development to combat antibiotic resistance under the leadership of the ZHAW.
ZHAW Impact 31/15 (German)
ZHAW-Medienmitteilung (German)
Organic Analysis + Structure Elucidation
We have the expertise and equipment for Analyses and Structure Elucidation of Organic Molecules of both routine in house samples or those of our customers, as well as ongoing research activities in the isolation, identification and optimization of biogenic drug molecules.
Cheminformatics
The goal of our activities in Cheminformatics is the development of IT solutions for the storage and convenient analysis of large data sets. Those data sets usually arise from medicinal chemistry projects. Here, the analysis of chemical structures in combination with effective and customizable displays of biological data are particularly useful, but large chemical inventory data sets of chemical organizations are also easily handled.
CyBy2: a structure-based data management tool for chemical and biological data
Research and Business Services
Collaborations
We offer a multitude of possible R & D collaborations. Long term CTI funded research projects are possible as well as mid-term contract research projects. Bachelor and Master Theses complement our research collaborations.
Medicinal Chemistry
- collaboration with research based pharmaceutical companies according to our complete set of medicinal chemistry capacities (from structure based design to organic synthesis and the delivery of small molecule clinical drug candidates)
- consulting in the area of medicinal chemistry and process management for start-up as well as small and mid-sized pharmaceutical companies (computational drug design, establishing screening concepts, development of structure activity relationships, development of clinical candidates, process optimization employing SixSigma process management tools)
Organic Synthesis and Organic Analytics
- development of multi-step organic synthetic routes employing a vast range of organic procedures, such as organocatalytic and organometallic catalysts
- evaluation of advanced synthetic techniques such as microreactor and microwave assisted organic syntheses, solid phase syntheses, biocatalytic processes and high pressure transformations
- NMR (1H, 13C, 19F, 31P and 2D measurements) and LC-MS measurements
- preparative HPLC purification
Cheminformatics
- adaption of our CyBy2 IT-solution as the central tool for your needs regarding data storage and data analysis of chemical and biological data sets
Technologies
Equipment
- Thermo MSQ Plus UHPLC‐single quadrupole system
- Liberty Blue Automated Microwave Peptide Synthesizer
- Bruker AVANCE III HD 500MHz OneBay NMR Spectrometer
- Waters Xevo-Acquity UPLC-triple quadrupole system
- Gilson PLC 2020 Purification system
- LC-MS Agilent Ion Trap XCT
- Knauer preparative HPLC System: flow rate up to 500 ml/min
- Ehrfeld and Little Things Factory semi-automatic microreactor synthesis equipment
- Radleys parallel synthesis equipment
- ISCO chromatography system
- GeneVac EZ-2 evaporation system
- 6-Core workstation equipped with molecular docking software
- lab reactor LabMax: automatic synthesis (-40 °C to 140 °C)
- ChemSpeed PSW 1100: automatic peptide synthesis equipment
- Biotage, MLS System: microwave assisted synthesis equipment
- Büchi autoclave systems: up to 50 bar and maximum 1 litre
- industry sized evaporation system Büchi R-220
- Perkin-Elmer 341 polarimeter, FTIR, GC
Awards
2013: SCG-FH Award Category «Molecules for the Life Sciences» Tackling antibiotic resistance: A joint project of the center for organic and medicinal chemistry ZHAW and the Bioversys AG.
SCG Webpage, ILMAC (more pictures), Poster
2013: SCS awarded the Dr. Max Lüthi award for bachelor thesis on the rational design and synthesis of novel protease inhibitors.
ZHAW press release (German)
2012: MSc thesis on the structure based design and synthesis of novel protease inhibitors received Bodenseeinnovation award.
ZHAW press release (German)
2011: SCS awarded the Dr. Max Lüthi award for bachelor thesis on ... über die Entwicklung von Wirkstoffen zur Bekämpfung von Antibiotikaresistenzen.
ZHAW press release (German)
Downloads
Strukturbasiertes Wirkstoffdesign (ChemiePlus 4/14, German)
Fighting the resistance (Pan European Networks Horizon 2020 Projects Portal 4/14)
Strategic Targeting of Multiple Water-Mediated Interactions: A Concise and Rational Structure-Based Design Approach to Potent and Selective MMP-13 Inhibitors (ChemMedChem 2013)
Bridging the disciplines (Pan European Networks: Science & Technology 7/2013)
Zielgerichtete Medikamente (Impact 3/13, German)
International Innovation Report (Interview and Report in International Innovation, 1/2013)
chemf: A purely functional chemistry toolkit (highly accessed, 20.12.12)
Rückblick auf den Chemie-Tag mit dem Thema Medizinalchemie (3. Wädenswiler Chemie-Tag, 2011, German)
Im Kampf gegen resistente Keime (20min Online, 15.05.11, German)
Wirkstoffdesign: Ein Molekül gegen Krebs (Impact 7/09, German)
Design and synthesis of novel scaffolds for therapeutically validated drug targets (Master Theses)