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Acoustic pipetting of nanoliter volumes for combinatorial chemistry and high-throughput screening

English title Acoustic pipetting of nanoliter volumes for combinatorial chemistry and high-throughput screening
Applicant Heinis Christian
Number 183443
Funding scheme R'EQUIP
Research institution Laboratoire de protéines et peptides thérapeutiques EPFL SB ISIC LPPT
Institution of higher education EPF Lausanne - EPFL
Main discipline Biochemistry
Start/End 01.12.2018 - 30.11.2020
Approved amount 240'000.00
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All Disciplines (2)

Discipline
Biochemistry
Organic Chemistry

Keywords (6)

drug development; macrocycle therapeutics; acoustic pipetting; combinatorial chemistry; high-throughput screening, HTS; liquid handling

Lay Summary (German)

Lead
Ein schnelles Transfer von sehr kleinen Volumen an Flüssigkeiten ist eine wichtige Voraussetzung für die kombinatorische Synthese von Molkülen wie sie in der Forschungsgruppe von Prof. Christian Heinis (EPFL) betrieben wird, und für das Screening von chemischen Substanzbibliotheken mit hohem Durchsatz an der Biomolekularen Screening Platform (BSF). Eine neue Technik basierend auf akustischen Wellen ermöglicht den Transfer von kleinsten Flüssigkeitsvolumen mit sehr hoher Geschwindikeit und grossem Durchsatz. Das vorliegende Projekt ermölicht die Anschaffung eines Gerätes welches auf dieser neuen Technologie aufbaut.
Lay summary

Das Labor von Christian Heinis entwickelt kombinatorische Methoden für die Synthese and das Screening von macrozyklischen Molekülen, mit dem Ziel der Herstellung von neuen Medikamenten gegen Zielproteine/Krankheiten für welche herkömmliche kleine Moleküle keine Lösungen bieten. Das Team von Christian Heinis hat neue chemische Reaktionen entdeckt welche geeignet sind um gleichzeitig tausende verschiedene Makrozyklische Moleküle zu synthetisieren. Das Labor setzt das neue Gerät dazu ein, sehr grossen Bibliotheken von makrozyklischen Molekülen herzustellen und zu testen.

Die Biomolekulare Screening Platform der School of Life Sciences der EPFL betreibt im Auftrag von verschiedenen Forschungsgruppen der EPFL und anderen Universitäten das hochdurchsatz Screening von Molekülen zur Identifizierung von bioaktiven Molekülen. Diese Arbeit basiert auf effizienten Flüssigkeits Transfer Systemen. Das BSF benütz das neue Gerät für diese Arbeiten.

Direct link to Lay Summary Last update: 11.12.2018

Responsible applicant and co-applicants

Project partner

Collaboration

Group / person Country
Types of collaboration
Roche Switzerland (Europe)
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Phage display selection of bicyclic peptidesthat survive oral administration Talk given at a conference Festival of Biologics European Antibody Congress 2020 02.11.2020 Basel, Switzerland Heinis Christian;
9th International Symposium on DNA-Encoded Chemical Libraries Talk given at a conference Phage Selection and High-Throughput Screening of Cyclic Peptides 06.09.2019 Zurich, Switzerland Heinis Christian;


Associated projects

Number Title Start Funding scheme
157842 Novel bioconjugation strategy and application for drug development 01.07.2015 SNSF Consolidator Grants
169526 Translating bicyclic peptides into therapeutics: Testing the therapeutic effect of a FXII inhibitor in three disease models 01.07.2017 Project funding (Div. I-III)
192368 Development and application of two general methods for creating orally applicable cyclic peptide therapeutics 01.07.2020 Project funding (Div. I-III)
160589 NCCR Chemical Biology: Visualisation and Control of Biological Processes Using Chemistry (phase II) 01.12.2014 National Centres of Competence in Research (NCCRs)

Abstract

Combinatorial synthesis projects carried out in the Laboratory of Therapeutic Peptides and Proteins (Institute of Chemical Sciences and Engineering, EPFL) led by Christian Heinis, and chemical screens performed at the Biomolecular Screening Facility (BSF) of EPFL and headed by Gerardo Turcatti are critically dependent on efficient automated liquid handling. A powerful technology to transfer nanoliter volumes at enormous speed and throughput is based on acoustic liquid dispensing and has become available in recent years. This project enables the purchase of an acoustic liquid handling system capable of transferring volumes ranging from 2.5 nL to 100 nL to wells of 384-well plates with a throughput of 100,000 transfers per day.The laboratory of Heinis is developing combinatorial methods to generate and screen macrocycle libraries with the aim of making drugs to challenging targets/diseases that proved not tractable by small molecules. The team has discovered new, powerful macrocyclization strategies that allow for the parallel synthesis of hundred thousands of macrocycles. The group of Heinis is applying the acoustic liquid handling system to generate and screen large combinatorial libraries of macrocyclic compounds.The BSF, a service platform of the School of Live Sciences (SV) of EPFL is screening large compound libraries in order to identify bioactive molecules needed by research labs at EPFL and other universities. This work depends on efficient liquid handling systems. The BSF is using acoustic liquid handling for small volume pipetting/dispensing in diverse projects.
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