Reference number : GC-2017-Q3-00555, amendment number : , agreement type : G, recipient legal name : Charette, André (Université de Montréal), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Engage Grants for universities, program name french : Subventions d'engagement partenarial pour les universités, program purpose english : Proteolysis-Targeting Chimeras (PROTACs) are bifunctional molecules that allow the elimination of target_x000D_
proteins --possibly responsible for various diseases-- by harnessing and bringing in a close range a ligase_x000D_
already present in the cells and triggering the proteolysis mechanism. Those synthetic entities are composed of_x000D_
3 main parts: a scaffold that is selective for the target in one end; a scaffold that is selective for the E3 ligase on_x000D_
the other end; and a linker that binds them together. Since 2008, new generations of PROTACs based on small_x000D_
molecule moieties have been developed, contrasting with earlier systems using large peptidic motifs and_x000D_
presenting several issues, notably their solubility and cell permeability._x000D_
Despite their advantages of this early field, the area of small molecules PROTACs presents some drawbacks_x000D_
and gray areas. Firstly, their syntheses can be long and tedious, especially concerning the central linker._x000D_
Secondly, the variety of those linkers is quite scarce, as poly-ether or alkyl chains are almost exclusively used._x000D_
Thirdly, their length variation and effects on the activity of the PROTACs are rarely studied._x000D_
The goals of this project are to: 1) develop new synthetic routes allowing the easier synthesis of various linkers_x000D_
using up-to-date technologies, such as automated supported synthesis, solid and soluble supports or flow_x000D_
chemistry; 2) develop new categories of linkers that will be tested for activity using standard POI and E3 ligase_x000D_
ligands; 3) combine those advances to allow the rapid synthesis of a wide range of linkers that will constitute a_x000D_
toolbox for next generation PROTACs., program purpose french : Proteolysis-Targeting Chimeras (PROTACs) are bifunctional molecules that allow the elimination of target_x000D_
proteins --possibly responsible for various diseases-- by harnessing and bringing in a close range a ligase_x000D_
already present in the cells and triggering the proteolysis mechanism. Those synthetic entities are composed of_x000D_
3 main parts: a scaffold that is selective for the target in one end; a scaffold that is selective for the E3 ligase on_x000D_
the other end; and a linker that binds them together. Since 2008, new generations of PROTACs based on small_x000D_
molecule moieties have been developed, contrasting with earlier systems using large peptidic motifs and_x000D_
presenting several issues, notably their solubility and cell permeability._x000D_
Despite their advantages of this early field, the area of small molecules PROTACs presents some drawbacks_x000D_
and gray areas. Firstly, their syntheses can be long and tedious, especially concerning the central linker._x000D_
Secondly, the variety of those linkers is quite scarce, as poly-ether or alkyl chains are almost exclusively used._x000D_
Thirdly, their length variation and effects on the activity of the PROTACs are rarely studied._x000D_
The goals of this project are to: 1) develop new synthetic routes allowing the easier synthesis of various linkers_x000D_
using up-to-date technologies, such as automated supported synthesis, solid and soluble supports or flow_x000D_
chemistry; 2) develop new categories of linkers that will be tested for activity using standard POI and E3 ligase_x000D_
ligands; 3) combine those advances to allow the rapid synthesis of a wide range of linkers that will constitute a_x000D_
toolbox for next generation PROTACs., agreement title english : Efficient Synthesis of a PROTAC Library Using Supported Chemistry and Automated/Continuous Flow Technologies, agreement title french : Efficient Synthesis of a PROTAC Library Using Supported Chemistry and Automated/Continuous Flow Technologies, agreement number : EGP, agreement value : 25000.0, agreement start date : 2017-10-18, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2018-2019)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada