Objective The main objective of the proposed project is the establishment of a generically-applicable new therapeutic molecule format, which will be referred as “bicyclic hetero peptidimer”. We propose linking two bicyclic peptides that bind to the same target but in different locations to generate an antagonist with high affinity and activity. This idea borrows from antibody therapeutics that typically have two arms that can bind to the target, increasing local concentration and improving the overall affinity of the therapeutic. In a second step, we will tether our active bicyclic hetero peptidimer to a known albumin-binding peptide to improve plasma half-life. This has previously been shown to increase the half-life of bicyclic peptides by nearly 50-fold in mice.In the proposed project we will use the new peptide format for the development of picomolar FXII inhibitors. Uncontrolled FXII activity is the cause for the severe disease hereditary angioedema (HEA), where currently no satisfactory therapeutic options are available. This general concept is in no way limited to any particular target, and has the potential to be generally applicable to any peptide-based therapeutics to increase both affinity as well as half-life, two of the major drawbacks to current peptide-based treatment strategies. Fields of science medical and health sciencesclinical medicinesurgerynatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesclinical medicinehematologynatural scienceschemical sciencesorganic chemistryamines Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Net EU contribution € 131 564,70 Address BATIMENT CE 3316 STATION 1 1015 Lausanne Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 131 564,70
