SNSF Consolidator Grant awarded to Prof. Christian Heinis
© 2015 Prof. Heinis
Prof. Christian Heinis has been awarded a CONSOLIDATOR GRANT by the SNSF in the context of the so-called “Temporary Backup Schemes” for the European Research Council (ERC) grants. This transitional measure of the SNSF offers the awardee an adequate substitute for an ERC grant.
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ChemBioDrug - Novel bioconjugation strategy and application for drug development
Bioconjugation methods are required for the development and/or manufacturing of many therapeutics as for example pegylated proteins or antibody-drug conjugates. Our laboratory is using bioconjugation reactions for the directed evolution of antagonist based on bicyclic peptides. A limitation of available bioconjugation reactions is the lack of site-selectivity. Existing conjugation reactions typically modify multiple amino acids of a single type in a protein or peptide (e.g. multiple lysines or multiple cysteines). For example several pegylated protein drugs and all clinically approved antibody-drug conjugates are randomly modified at multiple cysteine or lysine positions.
The aim of this project is to develop an entirely new, site-selective bioconjugation strategy and its application for the generation of peptide and protein therapeutics. The principle of the method is that only sites in a protein or peptide are chemically modified if a combination of two specific amino acids is present (e.g. lysine and cysteine).
I propose to apply the novel chemical conjugation strategy to three bioconjugation challenges in drug development: i) generation of proteolytically stable, orally available peptide drugs, ii) generation of antibody-drug conjugates with defined drug-to-antibody ratio, and iii) development of homogeneously pegylated therapeutic proteins.
Duration of the project: 60 months
Total amount: CHF 1’650’718.-
Domains: Natural Sciences, Organic Chemistry, Molecular Biology