Section for Organic and Medicinal Chemistry | ZHAW Institute of Chemistry and Biotechnology ICBT

«With our medicinal chemistry expertise, structure-based design and organic synthesis, we develop new treatment options for patients.»

Prof. Dr. Rainer Riedl, Head of Centre

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.

Research + Business Services

Awards + Publications

Networking

Team

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.)

Selected publications

Drug Design Inspired by Nature: Crystallographic Detection of an Auto‐Tailored Protease Inhibitor Template / F. M. Gall, D. Hohl, D. Frasson, T. Wermelinger, P. R. E. Mittl, M. Sievers, R. Riedl, Angew. Chem. Int. Ed. 2019, 58, 4051.
A Structural View on Medicinal Chemistry Strategies against Drug Resistance / S. Agnello, M. Brand, M. F. Chellat, S. Gazzola, R. Riedl, Angew. Chem. Int. Ed. 2019, 58, 3300.
Pseudouridimycin: The First Nucleoside Analogue That Selectively Inhibits Bacterial RNA Polymerase / M. F. Chellat, R. Riedl, Angew. Chem. Int. Ed. 2017, 56, 13184.
Targeting Antibiotic Resistance / Chellat, Mathieu; Raguž, Luka; Riedl, Rainer - Angew. Chem. Int. Ed. 2016, 55, 6600-6626; Angew.Chem. 2016, 128, 6710–6738.
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 / Fischer, Thomas; Riedl, Rainer - 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.
Merging Allosteric and Active Site Binding Motifs: De novo Generation of Target Selectivity and Potency via Natural-Product-Derived Fragments / Lanz, Jan; Riedl, Rainer - ChemMedChem. 2015, 10, 451–454. Front cover story 3/2015.
Strategic Targeting of Multiple Water-Mediated Interactions: A Concise and Rational Structure-Based Design Approach to Potent and Selective MMP-13 Inhibitors / Fischer, Thomas; Riedl, Rainer - ChemMedChem. 2013, 8, 1457-1461. Cover story 9/2013.

Publications

Gall, Flavio; Hohl, Deborah; Frasson, David; Wermelinger, Tobias; Mittl, Peer R. E.; Sievers, Martin; Riedl, Rainer,

2019.

Von der Natur inspiriertes Wirkstoffdesign : kristallographische Detektion eines selbstgenerierten Inhibitor‐Grundgerüsts.

Angewandte Chemie.

131(12), pp. 4091-4096.

Available from: https://doi.org/10.1002/ange.201812348
Agnello, Stefano; Brand, Michael; Chellat, Mathieu; Gazzola, Silvia; Riedl, Rainer,

2018.

Eine strukturelle Evaluierung medizinalchemischer Strategien gegen Wirkstoffresistenzen.

Angewandte Chemie.

131(11), pp. 3336-3383.

Available from: https://doi.org/10.1002/ange.201802416
Fischer, Thomas; Riedl, Rainer,

2013.

Strategic targeting of multiple water-mediated interactions : a concise and rational structure-based design approach to potent and selective MMP-13 inhibitors.

ChemMedChem.

8(9), pp. 1457-1461.

Available from: https://doi.org/10.1002/cmdc.201300278

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.

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.

Project

Natural Products Drug Discovery. A joint project within the ICBT.

(PDF 1,3 MB)

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

Projects

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02

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 CyBy²IT-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

Poster(PDF 891,1 KB) 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.
ZHAW press release(PDF 74,7 KB) (German) 2013: SCS awarded the Dr. Max Lüthi award for bachelor thesis on the rational design and synthesis of novel protease inhibitors.
ZHAW press release(PDF 46,8 KB) (German) 2012: MSc thesis on the structure based design and synthesis of novel protease inhibitors received Bodenseeinnovation award.
ZHAW press release (PDF 46,4 KB)(German) 2011: SCS awarded the Dr. Max Lüthi award for bachelor thesis on ... über die Entwicklung von Wirkstoffen zur Bekämpfung von Antibiotikaresistenzen.