High-throughput engineering of molecular glues
AssigneeFrontier Medicines Corporation
InventorsDaniel A. ERLANSON, Kevin Richard WEBSTER
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Abstract
The present disclosure relates generally to biological entity-protein (e.g. protein-protein) interactions for potential therapeutic applications, and more specifically to high-throughput methods for identifying bridging molecules that induce the formation of recruited biological entity-bridging molecule-target protein complexes to effect said biological entity-protein interactions. The present disclosure also provides methods for using said bridging molecules for treatment of disorders mediated by the target protein of the recruited biological entity-molecule-target protein complex.
Claims92
A method of identifying a bridging molecule that creates a recruited entity-molecule-target protein complex, comprising:
- selecting a target protein;
- selecting a template molecule known or predicted to bind to the target protein, said template molecule comprising one or more functional groups;
- derivatizing at least one of the one or more functional groups of the template molecule to form a library of derivatized template molecules;
- and
- screening the library of derivatized template molecules against a plurality of biological entities in the presence of the target protein.
A method of identifying a bridging molecule that creates a recruited entity-molecule-target protein complex, comprising:
- selecting a biological entity;
- selecting a template molecule known or predicted to bind to the biological entity, said template molecule comprising one or more functional groups;
- derivatizing at least one of the one or more functional groups of the template molecule to form a library of derivatized template molecules;
- and
- screening the library of derivatized template molecules against a plurality of target proteins in the presence of the biological entity.
A method of identifying a bridging molecule that creates a recruited protein-molecule-target protein complex, comprising:
- selecting a target protein;
- selecting a template molecule known or predicted to bind to the target protein, said template molecule comprising one or more functional groups;
- derivatizing at least one of the one or more functional groups of the template molecule to form a library of derivatized template molecules;
- and
- screening the library of derivatized template molecules against a plurality of proteins in the presence of the target protein.
A method of identifying a bridging molecule that creates a recruited protein-molecule-target protein complex, comprising:
- selecting a biological entity comprising a protein;
- selecting a template molecule known or predicted to bind to the biological entity, said template molecule comprising one or more functional groups;
- derivatizing at least one of the one or more functional groups of the template molecule to form a library of derivatized template molecules;
- and
- screening the library of derivatized template molecules against a plurality of target proteins in the presence of the biological entity.
A method for modulating the activity of a target protein, comprising:
- contacting the target protein with a bridging molecule in the presence of a recruited protein, wherein the target protein, bridging molecule and recruited protein form a recruited protein-molecule-target protein complex.
A method for modulating the activity of a target protein, comprising:
- contacting the target protein with a bridging molecule in the presence of a recruited entity, wherein the target protein, bridging molecule and recruited entity form a recruited entity-molecule-target protein complex.
Dependencies are inferred from the claim text.